Apparatus for control of non-invasive parameter measurements

ABSTRACT

Improved methods and apparatus for non-invasively assessing one or more parameters associated with fluidic systems such as the circulatory system of a living organism. In a first aspect, an improved method of continuously measuring pressure from a compressible vessel is disclosed, wherein a substantially optimal level of compression for the vessel is achieved and maintained using perturbations (e.g., modulation) of the compression level of the vessel. In one exemplary embodiment, the modulation is conducted according to a pseudo-random binary sequence (PBRS). In a second aspect, an improved apparatus for determining the blood pressure of a living subject is disclosed, the apparatus generally comprising a pressure sensor and associated processor with a computer program defining a plurality of operating states related to the sensed pressure data. Methods for pressure waveform correction and reacquisition, as well as treatment using the present invention, are also disclosed.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to methods and apparatus for monitoringparameters associated with circulating fluid systems, and specificallyin one aspect to the non-invasive monitoring of arterial blood pressurein a living subject.

2. Description of Related Technology

The accurate, continuous, non-invasive measurement of blood pressure haslong been sought by medical science. The availability of suchmeasurement techniques would allow the caregiver to continuously monitora subject's blood pressure accurately and in repeatable fashion withoutthe use of invasive arterial catheters (commonly known as “A-lines”) inany number of settings including, for example, surgical operating roomswhere continuous, accurate indications of true blood pressure are oftenessential.

Several well known techniques have heretofore been used tonon-invasively monitor a subject's arterial blood pressure waveform,namely, auscultation, oscillometry, and tonometry. Both the auscultationand oscillometry techniques use a standard inflatable arm cuff thatoccludes the subject's peripheral (predominately brachial) artery. Theauscultatory technique determines the subject's systolic and diastolicpressures by monitoring certain Korotkoff sounds that occur as the cuffis slowly deflated. The oscillometric technique, on the other hand,determines these pressures, as well as the subject's mean pressure, bymeasuring actual pressure changes that occur in the cuff as the cuff isdeflated. Both techniques determine pressure values only intermittently,because of the need to alternately inflate and deflate the cuff, andthey cannot replicate the subject's actual blood pressure waveforrn.Thus, continuous, beat-to-beat blood pressure monitoring cannot beachieved using these techniques.

Occlusive cuff instruments of the kind described briefly above havegenerally been somewhat effective in sensing long-term trends in asubject's blood pressure. However, such instruments generally have beenineffective in sensing short-term blood pressure variations, which areof critical importance in many medical applications, including surgery.

The technique of arterial tonometry is also well known in the medicalarts. According to the theory of arterial tonometry, the pressure in asuperficial artery with sufficient bony support, such as the radialartery, may be accurately recorded during an applanation sweep when thetransmural pressure equals zero. The term “applanation” refers to theprocess of varying the pressure applied to the artery. An applanationsweep refers to a time period during which pressure over the artery isvaried from overcompression to undercompression or vice versa. At theonset of a decreasing applanation sweep, the artery is overcompressedinto a “dog bone” shape, so that pressure pulses are not recorded. Atthe end of the sweep, the artery is is undercompressed, so that minimumamplitude pressure pulses are recorded. Within the sweep, it is assumedthat an applanation occurs during which the arterial wall tension isparallel to the tonometer surface. Here, the arterial pressure isperpendicular to the surface and is the only stress detected by thetonometer sensor. At this pressure, it is assumed that the maximumpeak-to-peak amplitude (the “maximum pulsatile”) pressure obtainedcorresponds to zero transmural pressure. Note that other measuresanalogous to maximum pulsatile pressure, including maximum rate ofchange in pressure (i.e., maximum dP/dT) can also be implemented.

One prior art device for implementing the tonometry technique includes arigid array of miniature pressure transducers that is applied againstthe tissue overlying a peripheral artery, e.g., the radial artery. Thetransducers each directly sense the mechanical forces in the underlyingsubject tissue, and each is sized to cover only a fraction of theunderlying artery. The array is urged against the tissue, to applanatethe underlying artery and thereby cause beat-to-beat pressure variationswithin the artery to be coupled through the tissue to at least some ofthe transducers. An array of different transducers is used to ensurethat at least one transducer is always over the artery, regardless ofarray position on the subject. This type of tonometer, however, issubject to several drawbacks. First, the array of discrete transducersgenerally is not anatomically compatible with the continuous contours ofthe subject's tissue overlying the artery being sensed. This can resultin inaccuracies in the resulting transducer signals. In addition, insome cases, this incompatibility can cause tissue injury and nervedamage and can restrict blood flow to distal tissue.

Other prior art techniques have sought to more accurately place a singletonometric sensor laterally above the artery, thereby more completelycoupling the sensor to the pressure variations within the artery.However, such systems may place the sensor at a location where it isgeometrically “centered” but not optimally positioned for signalcoupling, and further typically require comparatively frequentre-calibration or repositioning due to movement of the subject duringmeasurement.

Tonometry systems are also commonly quite sensitive to the orientationof the pressure transducer on the subject being monitored. Specifically,such systems show a degradation in accuracy when the angularrelationship between the transducer and the artery is varied from an“optimal” incidence angle. This is an important consideration, since notwo measurements are likely to have the device placed or maintained atprecisely the same angle with respect to the artery. Many of theforegoing approaches similarly suffer from not being able to maintain aconstant angular relationship with the artery regardless of lateralposition, due in many cases to positioning mechanisms which are notadapted to account for the anatomic features of the subject, such ascurvature of the wrist surface.

Furthermore, compliance in various apparatus components (e.g., the strapand actuator assembly) and the lack of soft padding surrounding thesensor which minimizes edge effects may adversely impact the accuracy oftonometric systems to a significant extent.

One very significant limitation of prior art tonometry approachesrelates to the magnitude and location of the applied applanationpressure during varying conditions of patient motion, position, meanpressure changes, respiration, etc. Specifically, even when the optimumlevel of arterial compression at the optimal coupling location isinitially achieved, there are commonly real-world or clinical factorsbeyond reasonable control that can introduce significant error into themeasurement process, especially over extended periods of time. Forexample, the subject being monitored may voluntarily or involuntarilymove, thereby altering (for at least a period of time) the physicalrelationship between the tonometric sensor and the subject'stissue/blood vessel. Similarly, bumping or jarring of the subject or thetonometric measurement apparatus can easily occur, thereby againaltering the physical relationship between the sensor and subject. Thesimple effect of gravity can, under certain circumstances, cause therelative positions of the sensor and subject blood vessel to alter withtime as well.

Furthermore, physiologic responses of the subject (including, forexample, relaxation of the walls of the blood vessel due to anesthesiaor pharmacological agents) can produce the need for changes in theapplanation level (and sometimes even the lateral/proximal position ofthe sensor) in order to maintain optimal sensor coupling. Additionally,due to the compliance of surrounding tissue and possibly measurementsystem, the applanation level often needs to adjust with changes in meanarterial pressure.

Several approaches have heretofore been disclosed in attempts to addressthe foregoing limitations. In one prior art approach, an occlusive cuffis used to provide a basis for periodic calibration; if the measuredpressure changes a “significant” amount or a determined time haselapsed, then the system performs a cuff calibration to assist inresetting the applanation position. Reliable pressure data is notdisplayed or otherwise available during these calibration periods. Seefor example U.S. Pat. No. 5,261,414 to Aung, et al issued Nov. 16, 1993and entitled “Blood-Pressure Monitor Apparatus,” assigned to ColinCorporation (hereinafter “Aung”). See also U.S. Pat. No. 6,322,516issued Nov. 27, 2001 and entitled “Blood-Pressure Monitor Apparatus,”also assigned to Colin Corporation, wherein an occlusive cuff is used asthe basis for calibration of a plurality of light sensors.

In another prior art approach, a pressure cuff or a pelotte equippedwith a plethysmographic gauge, such as an impedance or a photo-electricdevice, is used to drive a servo control loop. See, e.g., U.S. Pat. No.4,869,261 to Penaz issued Sep. 26, 1989 and entitled “Automaticnoninvasive blood pressure monitor,” assigned to University J.E. Purkynev Brne (hereinafter “Penaz”). In this device, the sensor is connectedthrough at least one amplifier and a phase corrector to anelectro-pressure transducer. All these components constitute the closedloop of a servo control system which (at least ostensibly) continuouslychanges the pressure in the cuff and attempts to maintain the volume ofthe artery at a value corresponding to zero tension across the arterialwall. The servo control system loop further includes a pressurevibration generator, the frequency of vibration being higher than thatof the highest harmonic component of blood pressure wave. A correctioncircuit is also provided, the input of which is connected to theplethysmographic sensor and output of which is provided to correct thesetpoint of the servo control system. The Penaz system therefore ineffect constantly “servos” (within a cardiac cycle) to a fixed lightsignal level received from the sensor. Unlike the Colin systemsdescribed above, the system continuously displays pressure to theoperator. However, the operation of the plethysmographic sensor of Penazlimited the application of this device to a peripheral section of a limb(preferably a fmger) where the peripheral pressure, especially underconditions of compromised peripheral circulation, may not accuratelyreflect aortic or brachial artery pressure. This presents a potentiallysignificant cause of error.

Yet another prior art approach uses a series of varying pressure“sweeps” performed successively to attempt to identify the actualintra-arterial blood pressure. The applanation pressure applied duringeach of these sweeps is generally varied from a level of arterialundercompression to overcompression (or vice-versa), and the systemanalyzes the data obtained during each sweep to identify, e.g., thelargest pressure waveform amplitude. See, e.g., U.S. Pat. No. 5,797,850to Archibald, et al issued Aug. 25, 1998 and entitled “Method andapparatus for calculating blood pressure of an artery,” assigned toMedwave, Inc. (hereinafter “Archibald”). The system of Archibald is nottruly continuous, however, since the sweeps each require a finite periodof time to complete and analyze. In practice the sweeps are repeatedwith minimal delay, one after another, throughout the operation of thedevice. During applanation mechanism resetting and subsequent sweepoperations, the system is effectively “dead” to new data as it analyzesand displays the data obtained during a previous sweep period. This isclearly disadvantageous from the standpoint that significant portions ofdata are effectively lost, and the operator receives what amounts toonly periodic indications of the subject's blood pressure (i.e., one newpressure beat display every 15-40 seconds).

Lastly, the techniques for non-invasive pressure measurement disclosedby the Assignee of the present invention in U.S. Pat. Nos. 6,228,034,6,176,831, 5,964,711, and 5,848,970, each entitled “Apparatus and methodfor non-invasively monitoring a subject's arterial blood pressure” andincorporated herein by reference in their entirety, include modulationof applanation level at, inter alia, frequencies higher than the heartrate (e.g., sinusoidal perturbation at 25 Hz). While the foregoingmethods are effective, Assignee has determined over time that it isdesirable at certain circumstances to control the applanation levelaccording to other modulation schemes and/or frequencies, and/or whichare not regular or deterministic in nature. Furthermore, certainmodulation schemes (e.g., intra-beat modulation) can place significantdemands on the applanation hardware, since more rapid (and oftenprecise) variations in applanation level must occur. Accordingly, themore capable hardware required in such applications ultimately raisesthe cost of the parent device in which it is used.

Based on the foregoing, there is needed an improved methodology andapparatus for accurately and continuously controlling the non-invasivemeasurement of parameters such as pressure. Such improved methodologyand apparatus would ideally allow for, inter alia, continuousmeasurement (tonometrically or otherwise) of one or more hemodynamicparameters, the measured values of such parameters being reflective oftrue intra-arterial parameters, while also providing robustness andrepeatability under varying environmental conditions including motionartifact and other noise. Such method and apparatus would also be easilyutilized by both trained medical personnel and untrained individuals,thereby allowing subjects to accurately and reliably conductself-monitoring if desired.

SUMMARY OF THE INVENTION

The present invention satisfies the aforementioned needs by improvedmethods and apparatus for non-invasively and continuously controllingthe measurement of parameters in a fluidic system, including arterialblood pressure within a living subject.

In a first aspect of the invention, an improved method of continuouslymeasuring pressure from a compressible vessel is disclosed, the methodgenerally comprising: disposing a pressure sensor in proximity to thevessel; identifying a substantially optimal level of compression for thevessel; achieving the substantially optimal level of compression;measuring pressure data from the vessel using the sensor; identifyingnon-optimal levels of compression; and adjusting applanation to maintainor reacquire the optimal level of compression. In one exemplaryembodiment, the sensor is applied tonometrically, and the method ofmaintaining optimal level of compression comprises at least periodicallyperturbing the level of compression of the vessel during the act ofmeasuring to produce an observable effect on the measured pressure data;and adjusting the level of compression based at least in part on theeffect. In one exemplary embodiment, the vessel comprises a bloodvessel, and the applied perturbations comprises pseudo-random binarysequences which are used to modulate the level of compression applied tothe vessel over time. Effects on the sensed pressure are correlated tothe modulation, and necessary corrections applied thereto.

In a second aspect of the invention, an improved apparatus fordetermining the blood pressure of a living subject is disclosed, theapparatus generally comprising: a tonometric pressure sensor deviceadapted for sensing the pressure at the skin surface of a living subjectand generating pressure data relating thereto; and a processor adaptedto run a computer program thereon, the computer program defining aplurality of operating states, the use of each of the operating statesby the apparatus in determining blood pressure being related at least inpart to the pressure data In one exemplary embodiment, the computerprogram comprises three (3) distinct sub-processes relating to transientdetection and compensation, servoing (or slower-rate changes tocoupling), and reacquisition after loss of coupling, respectively. Thefirst process in this exemplary embodiment employs four (4) distinct butrelated states which govern applanation and lateral/proximalpositioning.

In a third aspect of the invention, a method of modulating tonometricblood pressure measurements is disclosed. The method generallycomprises: providing a transducer adapted for determining pressure, thetransducer being disposed proximate a blood vessel; and varying thelevel of compression applied to the blood vessel over time, the act ofvarying comprising modulating the level of compression. In an exemplaryembodiment the modulation operates according to a modulation sequence,wherein the modulation sequence comprises a PRBS as previouslydescribed, although other random or deterministic sequences may be used.

In a fourth aspect of the invention, a method of correcting tonometricpressure measurements is disclosed, the method generally comprisingproviding a transducer adapted for determining pressure, the transducerdisposed proximate to a blood vessel; varying the level of compressionapplied to the blood vessel over time; measuring pressure from the bloodvessel using the transducer, and correcting the measured pressure basedat least in part on the correlation between the acts of varying andmeasuring. In the exemplary embodiment, the aforementioned modulationsequence is used to generate effects within the sensed pressurewaveform; these effects are correlated to the modulation sequence andcorrections to the sensed pressure values generated based thereon.

In a fifth aspect of the invention, an improved apparatus for measuringthe blood pressure within a blood vessel is disclosed. The apparatusgenerally comprises: a tonometric pressure sensor adapted for sensingthe pressure at the skin surface of a living subject and generating anelectrical signal relating thereto; a signal converter adapted toconvert the electrical signal to the digital domain; a digital processorin data communication with the converter; a computer program adapted torun on the digital processor, the program being further adapted tomodulate the position of the tonometric sensor over time according tothe aforementioned modulation sequence. In one exemplary embodiment, anapplanation apparatus controlled by the computer program is coupled tothe pressure sensor, and the level of applanation varied according tothe modulation sequence. In another embodiment, the lateral and/orproximal position of the sensor is controlled using a comparablemodulation scheme.

In a sixth aspect of the invention, an improved method of identifyingchanges in the coupling between a tonometric sensor and the tissue of asubject is disclosed, the method generally comprising: disposing thesensor in proximity to the tissue; measuring data from the tissue usingthe sensor; and identifying at least one change in a parameterassociated with the coupling based at least in part on the measureddata. In one exemplary embodiment, the measured parameters includepressure velocity and acceleration.

In a seventh aspect of the invention, a transient-resistant apparatusfor determining the blood pressure of a living subject is disclosed. Theapparatus generally comprises a tonometric pressure sensor adapted forsensing the pressure at the skin surface of a living subject andgenerating a waveform relating thereto; motive apparatus adapted toreposition the pressure sensor; a controller operatively coupled to themotive apparatus; and a processor in data communication with the sensorand operatively coupled with the controller, the processor adapted torun a computer program thereon, the computer program being configured to(i) establish an initial substantially optimal position of the sensorfor at least one epoch; (ii) measure pressure data from the blood vesselusing the sensor; (iii) detect the occurrence of a transient event byanalyzing changes in the pressure data, the transient event altering thecoupling between the blood vessel and sensor; (iv) initiate a sensorsweep via the controller and motive apparatus to identify a secondsubstantially optimal sensor position based on the altered coupling; and(v) establish the second substantially optimal sensor position for atleast one epoch.

In an eighth aspect of the invention, an improved method of identifyingchanges in the coupling between a tonometric pressure sensor and thetissue of a subject during a blood pressure measurement based onparticular portions of the cardiac cycle is disclosed. The methodgenerally comprises: disposing the sensor in proximity to the tissue;measuring pressure data from the tissue using the sensor; determining atleast one parameter from the data; comparing the at least one parameterto a criterion, the criterion being determined at least in part by theportion of the cardiac cycle during which the pressure data wasmeasured; and identifying a change in coupling based at least in part onthe act of comparing. In one exemplary embodiment, the parametercomprises both pressure velocity and acceleration, and the criterioncomprises threshold values for each relating to either the systolic(upstroke) or diastolic (downstroke) portions of the cardiac cycle.

In a ninth aspect of the invention, an improved method of maintaining anoptimal or near-optimal level of compression (or alternatively,position) for a blood pressure measuring apparatus is disclosed. Themethod generally comprises using a correlation process to analyze curvesexisting in relation to a “target”, the curves relating pressure as afunction of a spatial position parameter. In one exemplary embodiment,the pressure comprises pulse pressure and/or diastolic pressure, and thespatial position parameter comprises motor position (e.g., applanation,lateral, or proximal drive motor). The method analyzes the slope of thecurves by, inter alia, obtaining a first derivative (e.g., d(PulsePressure)/d(Motor Position) and/or d(Diastolic Pressure)/d(MotorPosition)), and correlates these slope values to identify the optimal ornear-optimal “target” position.

These and other features of the invention will become apparent from thefollowing description of the invention, taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a state diagram illustrating the relationship of the fourstates associated with a first exemplary embodiment of the first processof the present invention.

FIG. 1 a is logical flow diagram illustrating the operation of theexemplary embodiment of the first process of FIG. 1.

FIG. 2 is logical flow diagram illustrating the operation of oneexemplary embodiment of the second process (e.g., servoing ormaintaining optimal applanation level) according to the invention.

FIG. 2 a is a graph of pulse pressure versus diastolic pressure for anexemplary patient.

FIG. 2 b is a graph of tonometric pressure versus time for the optimalarterial compression (applanation) of the patient of FIG. 2 a.

FIG. 2 c is a graph of tonometric pressure versus time for both optimaland non-optimal applanation level applied to the patient of FIG. 2 a.

FIG. 2 d is a graph of an exemplary embodiment of the modulation schemeaccording to the present invention, illustrating the PRBS modulationvalue versus applanation motor step number.

FIG. 2 e is a graph of the tonometric pressure obtained from the patientof FIG. 2 a with and without PRBS modulation applied to non-optimalapplanation, illustr ing the effects of PRBS modulation.

FIG. 2 f is a graph of the corrected or restored tonometric pressurewaveform after application of PRBS modulation to the non-optimalapplanation profile.

FIG. 2 g is a graph of an exemplary embodiment of the PRBS modulation ofthe invention (PRBS length=7), illustrating the correlation betweenmodulation and corrected pulse pressure.

FIG. 2 h is a graph of pressure versus beat number illustrating thecorrelation between the weighted zero mean values for exemplary pulsepressure and diastolic pressure, and PRBS modulation.

FIG. 2 i is a graph of pressure versus phase delay for pulse pressure,diastolic pressure, and PRBS modulation according to one embodiment ofthe invention.

FIG. 3 is a logical flow diagram illustrating one exemplary embodimentof the method of determining the optimal initial modulation according tothe present invention.

FIGS. 3 a and 3 b are graphs illustrating various aspects of thecalculations supporting the methodology of FIG. 3.

FIG. 4 is logical flow diagram illustrating the operation of oneexemplary embodiment of the third process (e.g., reacquisition)according to the invention.

FIG. 4 a is a graphical illustration of an exemplary embodiment of thefourth (“sweep”) state entry criteria associated with the third processof the invention.

FIG. 5 is a block diagram of one exemplary embodiment of the apparatusfor measuring hemodynamic parameters within the blood vessel of a livingsubject according to the invention.

FIG. 6 is a logical flow diagram illustrating one exemplary embodimentof the method of providing treatment to a subject using theaforementioned methods.

DETAILED DESCRIPTION OF THE INVENTION

Reference is now made to the drawings wherein like numerals refer tolike parts throughout.

It is noted that while the invention is described herein primarily interms of a method and apparatus for the control of non-invasivemeasurements of hemodynamic parameters such as blood pressure obtainedvia the radial artery (i.e., wrist) of a human subject, the inventionmay also be readily embodied or adapted to monitor such parameters atother blood vessels and locations on the human body, as well asmonitoring these parameters on other warm-blooded species. Similarly,the techniques of the present invention can be applied to other similarfluidic systems which have similar properties to those of thecirculatory system of a living being. All such adaptations and alternateembodiments are readily implemented by those of ordinary skill in therelevant arts, and are considered to fall within the scope of the claimsappended hereto.

As used herein, the term “hemodynamic parameter” is meant to includeparameters associated with the circulatory system of the subject,including for example pressure (e.g., diastolic, systolic, pulse, ormean pressure), derivatives or combinations thereof, arterial flow,arterial wall diameter (and its derivatives), cross sectional area ofthe artery, and arterial compliance.

Additionally, it is noted that the terms “tonometric,” “tonometer,” and“tonometery” as used herein are intended to broadly refer tonon-invasive surface measurement of one or more hemodynamic parameters,such as by placing a sensor in communication with the surface of theskin, although contact with the skin need not be direct, and can beindirect (e.g., such as through a coupling medium or other interface).

The terms “applanate” and “applanation” as used herein refer to thecompression (relative to a state of non-compression) of tissue, bloodvessel(s), and other structures such as tendon or muscle of thesubject's physiology. Similarly, an applanation “sweep” refers to one ormore periods of time during which the applanation level is varied(either increasingly, decreasingly, or any combination thereof).Although generally used in the context of linear (constant velocity)position variations, the term “applanation” as used herein mayconceivably take on any variety of other forms, including withoutlimitation (i) a continuous non-linear (e.g., logarithmic) increasing ordecreasing compression over time; (ii) a non-continuous or piece-wisecontinuous linear or non-linear compression; (iii) alternatingcompression and relaxation; (iv) sinusoidal or triangular wavesfunctions; (v) random motion (such as a “random walk”; or (vi) adeterministic profile. All such forms are considered to be encompassedby the term.

As used herein, the term “epoch” refers to any increment of time,ranging in duration from the smallest measurable fraction of a second tomore than one second.

As used herein, the terms “spatial” and “position”, although describedin terms of a substantially Cartesian coordinate system havingapplanation (i.e., Z-axis), lateral (X-axis) and (Proximal refers tocloser to the heart) longitudinal or (proximal—distal) (Y-axis)components, shall refer to any spatial coordinate system including,without limitation, cylindrical, spherical, and polar. Such use ofalternate coordinate systems may clearly be independent of anyparticular hardware configuration or geometry (e.g., by performingsimple mathematical translations between a Cartesian-based apparatus andthe non-Cartesian coordinate system), or alternatively make advantageoususe of such geometries. The present invention is therefore in no waylimited to certain coordinate systems of apparatus configurations. Asone example, it will be recognized that the methods and apparatus of thepresent invention may be embodied using a cylindrical coordinate systemmodeled around the radial artery, such that a particular point in spacefor the tonometric sensor(s) can be specified by the Z, r, and 0parameters. This approach may have advantages since the forearm/wristarea of the human being very roughly comprises a cylindrical form.

Lastly, the term “digital processor” is meant to include any integratedcircuit or other electronic device (or collection of devices) capable ofperforming an operation on at least one instruction including, withoutlimitation, reduced instruction set core (RISC) processors such as thosemanufactured by ARM Limited of Cambridge, UK, CISC microprocessors,microcontroller units (MCUs), CISC-based central processing units(CPUs), and digital signal processors (DSPs). The hardware of suchdevices may be integrated onto a single substrate (e.g., silicon “die”),or distributed among two or more substrates. Furthermore, variousfunctional aspects of the processor may be implemented solely assoftware or firmware associated with the processor.

Overview

In one findamental aspect, the present invention comprises methods andapparatus for controlling an applanation or other positioning mechanismused in non-invasive hemodynamic parameter measurements in order to,inter alia, maintain optimal coupling between a parameter sensor and theblood vessel of interest. Techniques for determining the optimalapplanation level, position, and coupling are described in detail in,e.g., co-pending U.S. patent application Ser. No. 10/072,508 entitled“Method And Apparatus For Non-Invasively Measuring HemodynamicParameters Using Parametrics” filed Feb. 5, 2002, which is assigned tothe Assignee hereof and incorporated by reference herein in itsentirety.

While the techniques described in the aforementioned co-pending patentapplication have been determined by Assignee to be highly effective,their robustness and utility in practical (e.g., clinical) settings isenhanced through the addition of one or more of the various aspects ofthe present invention. Such additional robustness is highly desirable,since it effectively removes many operational restrictions on aclinician, caregiver, or user (hereinafter “operator”) when measuringhemodynamic parameters such as blood pressure. Specifically, theoperator is substantially relieved of having to monitor the signalderived from the measurement apparatus to detect anomalies, motionartifact, and under certain circumstances will even identify to theoperator when error conditions which cannot be corrected have in factoccurred.

After the applanation and lateral (and proximal, if desired) positionsthat provide the optimal mechanical coupling between the system sensorand the underlying blood vessel have been determined, the invention ofthe present disclosure is used to control and adjust the level ofapplanation and/or the lateral/proximal positions to maintain theoptimal coupling under potentially adverse environmental conditions suchas might be encountered in the average clinical setting. Due to thenature of the clinical setting and all of its variables, not everyenvironmental condition or influence can always be compensated for, andhence the present invention has as another function the ability toidentify conditions where changes in mechanical coupling have impactedthe accuracy or reliability of hemodynamic measurements in a meaningfulmanner.

Three separate but substantially interactive processes are used in thepresent invention to provide the aforementioned control andidentification functionalities: (i) a first process adapted to identifysudden changes in the mechanical coupling, as indicated for example bychanges in the measured parameter (such as tonometrically measuredpressure or pressure velocity) that exceed expected norms, and reacquireeither/both the optimal applanation level or lateral/proximal positionswhere appropriate; (ii) a second process adapted to continuouslyidentify time varying changes in compression coupling, and controllablyadjust the applanation position accordingly (“servoing”); and (iii) athird process adapted to operate interactively with the first state andprovide warning and protection against loss of optimal coupling in oneor more domains, as well as performing a new determination(s) of optimalposition in an optimized fashion.

The techniques and apparatus of the present invention may be used with asingle sensor (or array of sensors) as described in detail herein andthe aforementioned and incorporated co-pending application, or inconjunction with literally any type of other apparatus adapted forhemodynamic parameter measurement, including for example the devicesdescribed in co-pending U.S. patent application Serial Nos. 09/815,982entitled “Method and Apparatus for the Noninvasive Assessment ofHemodynamic Parameters Including Blood Vessel Location” filed Mar. 22,2001, and 09/815,080 entitled “Method and Apparatus for AssessingHemodynamic Parameters within the Circulatory System of a LivingSubject” also filed Mar. 22, 2001, both of which are assigned to theassignee hereof and incorporated herein by reference in their entirety.For example, ultrasound measurements of blood pressure via blood flowkinetic energy or velocity can be used as a confirmatory technique for afundamentally tonometric pressure-based approach. As another example,lateral positioning based on analysis of the acoustic signals relatingto vessel wall detection may be used in addition to (or in place of) thepressure-based techniques described in the originally cited co-pendingpatent application. Hence, the various aspects of the present inventionare advantageously compatible with a number of different hemodynamicassessment techniques. It will also be recognized that the techniquesand apparatus described herein are in no way limited to tonometricapplications; rather, these features may be implemented even inocclusive cuff or pellot-based systems.

Since signals under measurement (e.g. pressure) are time variant,iteration and optimization are substantially used by the methodology ofthe present invention to account for this variation. Specifically, thepressure signal associated with a blood vessel is time variant over theshort period of the cardiac cycle, over the longer period of therespiratory cycle, and potentially over the even longer or shorterperiod of hemodynamic changes resulting from varying drug concentrationsand volume changes. Accordingly, the three processes referenced aboveutilize the aforementioned applanation and lateral/proximal positioningmechanisms to continually find and maintain the optimal position andlevel of applanation, thereby maintaining an environment conducive foraccurate, continuous, and non-invasive parametric measurement. In thosevery limited circumstances where such optimal position and level cannotbe reasonably or reliably maintained (such as an abrupt and jarringdislocation of the apparatus from the subject's anatomy), the presentinvention identifies such conditions accordingly, and optionally alertsthe operator or provides other notification.

Table 1 below summarizes the functionality and features of one exemplaryembodiment of the invention incorporating the three aforementionedprocesses. TABLE 1 Feature First Process Second Process Third ProcessDetection Time Frequency of >5 Hz All Frequencies >20 Seconds ChangesRecovery Method Applanation Sweep Continuous Adjustment ApplanationSweep Time to Recover 10-20 seconds 20-120 seconds 10-20 seconds(Largely Uncorrelated to (Correlated to (Largely Uncorrelated toMagnitude of error) Magnitude of error) Magnitude of error)Lateral/Proximal Search Possible No No Pressure Display Continuous No:Recovery Sweeps Yes No: Recovery SweepsDescription of First Process

Referring now to FIG. 1-1 a, a first exemplary embodiment of the methodof identifying sudden changes in the mechanical coupling andreacquisition of either/both the optimal applanation level orlateral/proximal positions according to the invention is described indetail. A detailed discussion of the electronic and signal processingapparatus used to support the operation of the processes describedherein is provided with respect to FIG. 5 below. It will be appreciatedthat while portions of the following discussion are cast in terms ofapplanation (and lateral/proximal positioning) motors of thestepper-type, the techniques of the present invention may be utilized inconjunction with other types of applanation and positioning apparatus,and accordingly are in no way limited to the specific embodiments ofapparatus described herein.

It will also be recognized that while the first process is describedsubsequently herein with respect to a tonometric pressure transducer,the methodology of the invention can be applied more generally to othersignal domains. For example, sudden changes in the mechanical couplingof an ultrasonic transducer to a subject's tissue can be identifiedusing, inter alia, parameters which exceed physiological norms asindicia thereof or measureable distortion in the measurement process.Sudden changes in 5 mechanical coupling will alter the measurement ofmany parameters, both physiological in nature and otherwise.

Furthermore, it will be appreciated that while described in the contextof the aforementioned apparatus (i.e., a tonometric pressure sensorwhich also acts to provide varying levels of compression of theunderlying tissue and blood vessel(s)), the methodology of the presentinvention may be practiced using apparatus having separate componentswhich provide these functions. For example, the control of the pressuresensor may be partly or completely decoupled from the applanationcontrol system, such that the level of applanation can be variedindependently from the coupling of the active surface(s) of the sensor.The first process of the present embodiment continuously checks for(sudden) changes in the mechanical coupling between a tonometricpressure sensor and the underlying vessel/tissue. Sudden changes inmechanical coupling can be identified by corresponding sudden changes intonometrically derived pressure P_(T) (first or second derivative ofpressure) that exceed physiologic norms. A velocity parameter, Vp[k], iscalculated as in Eqn. 1:P _(T) [k]−P _(T) [k-3]  (Eqn. 1)where k represents the current sample, k−3 represents three samples inthe past where the sample rate is 160 Hz. Tonometrically measuredacceleration, Ap[k], is calculated as in Eqn. 2:Vp[k]−Vp[k-1]=P _(T) [k]+P _(T) [k-4]−(P _(T) [k-1]+P _(T) [k-3])  (Eqn.2)For each sample the pressure, velocity and acceleration are comparedwith fixed (or deterministic) thresholds. If any one of these parametersexceeds their respective thresholds, then a process “event” istriggered. Note that the pressure, velocity, and acceleration aretypically greater during the systolic pressure upstroke than during thediastolic pressure downstroke, hence the thresholds of the presentembodiment are set accordingly, providing effectively a “buffer” betweenphysiologic norms and process event triggers. This buffer enhancessystem robustness, in that trigger events occurring at physiologic normsare avoided.

For example, the ranges of velocity and acceleration of a patient'sblood pressure should fall within some limits around zero (generally notsymmetric). Changes in mechanical coupling could also be observed aschanges (velocity or acceleration) in tonometrically observed pressure.The first process 100 focuses on those changes in mechanical couplingthat are both comparatively large and rapid, thus producing velocity oracceleration values that are not realizable from the patient's arterialpressure alone. The buffer of the present embodiment comprises that“cushion” between the range of measurable velocity and acceleration thatis naturally occurring (from patient's arterial pressure) and thetrigger threshold for the first process 100. It will be recognized,however, that such buffer or cushion may be at least partly obviatedthrough use of one or more sensors that specifically measure changes inmechanical coupling, such as for example a pad sensor, which would allowthe system to identify and possibly respond to smaller changes and/orlower frequency changes in mechanical coupling.

When sudden changes in mechanical coupling are detected, tonometricpressure data are compared for periods occurring before and after theprocess event. For instance, if the pulse pressure (defined for thepresent discussion as the difference between systolic and diastolicpressures) decreases from the maximum, or the mean pressure changessignificantly, then a limited scope pressure sweep is implemented toachieve the optimal applanation. If, despite this pressure sweep, acomparable pulse pressure is not achieved, then a reacquisition state(described in greater detail below) must be entered.

Note that in the present embodiment, the first process is active exceptin conditions where the system initialization, initial lateral searchand applanation sweeps are being performed or when operating in theaforementioned reacquisition state. The second process is also active atthe same time as the first process, except in conditions where the firstprocess is performing the limited scope pressure sweep as previouslydescribed. It will also be noted that during the limited scope pressuresweep, the current value of P_(T) is not displayed. Excessive periods,where the current P_(T) is not available limits the clinical utility ofthe device, as previously described herein with respect to the priorart. Thus, the present invention minimizes the need for the limitedscope pressure sweeps invoked by a process event, thereby improving theoverall performance and continuity of the technique over prior artsolutions.

The first process 100 of the present embodiment consists of 4 discretebut related states 102, 103, 104, 105 as illustrated in FIG. 1; (i)first state (“normal operation”) 102; (ii) second state (“event”) 103;(iii) third state (“recovery”) 104; and (iv) fourth state (“sweep”) 105.The impact of a process event on the servo control system (described ingreater detail below with respect to FIGS. 2 and 5), depends largely onthe then-exiting state. Each of these four process states 102-105 arenow described in detail.

(i) First (Normal Operation) State—The first state 102 is the initialand default operating state. This state is entered when a sweepcompletes, or following the detection of a sudden change in mechanicalcoupling little change was observed between pre- and post-pressure data.If a process event occurs, then the most recent median filteredtonometric mean and pulse pressures are stored for future comparisons. Atemporal parameter (e.g., Time_of_Last_Event) is set to zero (units inseconds), and the process state is set to the second state (event). Ifno process event is detected, the first state (normal operation) ismaintained. Note that in the present embodiment, the second process 200(i.e., servoing, discussed below with respect to FIGS. 2-2 i) is activeduring this first normal operating state 102.

(ii) Second (Event) State—The second or event state 104 indicates thatone or more process events 106 has recently occurred, and the system iswaiting for the perturbations relating to the event(s) to subside beforeentering the next state. If a process event occurs then, the temporalparameter (e.g., Time_of_Last_Event) is reset. However, if a sufficienttime ( i.e., 2 seconds) has elapsed since the last event (as determinedby the existing value Time_of_Last_Event), then the beat counter(Beat_Counter) value is initialized for comparisons, and the process isset to the third (recovery) state. The prescribed time delay of thepresent embodiment advantageously minimizes the risk of corruptedpressure data from being incorporated in the post-process event pressuredata. As in the first state described above, the second process(servoing) is active during the second state 103.

(iii) Third (Recovery) State—Entry into this third state 104 indicatesthat the recent process event has subsided, and the system is collectingnew tonometric beat pressure data to compare with pre-perturbation data.Upon exit from the third state 104 and before entering the next state,if a process event occurs, then the Time_of_Last_Event parameter isreset, and the process state is set to the second (event) state 103 perstep 108. Otherwise, if a new tonometric beat has been identified then,the system beat counter parameter (e.g., Beat_Counter) is incrementedfor comparisons, and new mean and pulse pressures are written to thestorage device (FIG. 5) for subsequent comparisons.

Note that if the beat counter has reached a predetermined thresholdvalue, then a comparison of the tonometric pulse and mean pressuresstored both before and after the triggering process event is performed.If, upon performing this comparison, the mean pressure has changedbeyond a predetermined threshold, or the pulse pressure has decreasedsubstantially from pre- to post-event, then the state of the process 100is set to the fourth (i.e., sweep) state 105, the sweep initializationparameter (e.g., Initialize₁₃ Sweep) is set to “true”, and the secondprocess (servoing) is disabled. The motor position parameter (e.g.,Motor_Position) is accordingly set to a target motor position value.Target motor position in the illustrated exemplary embodiment is set toeither 0 (fully retracted) or −50000 (fully extend out toward the radialartery) where units are motor steps. Target motor position is set to 0if the post-event mean pressure is greater than the pre-event meanpressure. Target motor position is set to −50000 if the post-event meanpressure is less than the pre-event mean pressure. If the mean pressurehas not increased beyond the threshold (and the pulse pressure has notdecreased substantially between pre- and post-event), the state of thefirst process 100 is set to the normal operating (first) state 102 perstep 110 of FIG. 1.

If the beat counter has not reached its predetermined threshold, thefirst process 100 remains in the third (recovery) state 104. As with thefirst and second states 102, 103 described above, the second (servoing)process 200 remains, in the illustrated embodiment, active during therecovery state 104.

(iv) Fourth (Sweep) State—Entry into this fourth state 105 indicatesthat the recent process event has caused a significant change in thetonometrically measured pulse pressure and/or mean pressure. Inresponse, the system performs a limited scope pressure sweep to resetthe optimal applanation level. Specifically, if the sweep initializationvariable (Initialize_Sweep) is set true, the initial search direction asdetermined for target motor position in (iii) above, and the applanationmotor(s) are moved in the proper direction (ramp continuously in thepresent embodiment, although other profiles may be used). Additionally,the sweep pressure memory is initialized, and the “first pass” parameterflag (e.g., FirstPass_Flag) is set to “true.”

If a new beat has been identified, then the process appends thetonometric pressure data associated with the new beat to that existingin the memory array and the Beat_Counter value is incremented forcomparisons. Specifically the data for each beat includes averageapplanation position, mean tonometrically measured pressure, systolictonometric pressure, diastolic tonometric pressure, and tonometric pulsepressure (i.e., systolic minus diastolic), which are stored inparameter-specific one dimensional arrays within memory.

If the measured mean pressure has reached its minimum goal and currentpulse pressure values (median filtered) are significantly less thanmaximum pulse pressures (median filtered) observed during the sweep,then additional analysis is performed. Specifically, if the maximumpulse occurred close to beginning of the applanation sweep, and thefirst pass flag (FirstPass_Flag) equals “true” then the FirstPass_Flagis set to “false”, and the applanation motor(s) are moved, e.g., to rampcontinuously, in the direction opposite from the prior direction oftravel. If the maximum pulse pressure did not occur near the beginningof the sweep, and if the maximum pulse pressure (median filtered) is alarge percentage (e.g., 80% or greater in the present embodiment) ofthat occurring prior to the triggering event then the state of theprocess 100 is set to the first state 102, and servoing at the maximumpulse pressure is initialized. In the context of the present embodiment,the measured mean pressure reaching its “minimum goal” comprises themedian filtered mean pressure at least reaching and searching beyond thepre event trigger mean pressure. Note that this requirement can bedependent on the direction of the search (i.e., whether extending orretracting the sensor); specifically, the median filtered mean pressureis greater than the pre-event trigger mean pressure for the sensorextension case, or less than the pre-event trigger mean pressure for theretraction case.

However, if the maximum pulse pressure occurs not near the beginning,and the maximum pressure value is not a large percentage of the prioroccurring value, then the reacquisition process (the third process 400discussed below with respect to FIG. 4) is entered, and the firstprocess 100 is disabled.

It is also noted that second process 200 (FIG. 2) is not active duringthe fourth state 105 of the first process 100.

FIG. 1 a provides a detailed flow chart representation of the exemplaryfirst process 100 of FIG. 1.

It will further be recognized that the first process 100 may be appliedto blood pressure measurements irrespective of the mechanism used tooriginally attain optimal applanation position. In this scenario, thefirst process operates effectively as if a large transient event hadoccurred, and uses the foregoing method (in conjunction with the thirdor reacquisition process 400 described below with respect to FIG. 4) tosettle onto optimal positions for these parameters.

It will be recognized that as referenced above, the first process of thepresent invention need not operate using a “physiologic” parameter. Oneexemplary alternative approach of the present invention is to apply andaccelerometer or force transducer of the type well known in the art onor contiguous with the sensor surface; i.e., not necessarily over theblood vessel of interest itself. Similarly, such accelerometer ortransducer may be located on the apparatus coupling the sensor to thepatient (e.g., wrist brace or strap), or alternatively on the shaft (notshown) between the actuating mechanism and the sensor/pad (or within theactuating mechanism itself). Since the first process of the presentinvention fundamentally detects rapid motion corresponding to potentialmechanical coupling disruptions, literally any physical configurationand/or parameter which provides information relating to such motion anddisruptions may be used consistent with the invention. As yet anotheralternative embodiment, an optical sensor of the type well known in theelectronic arts may be positioned near the skin and accordingly used asthe mechanism to detect sudden changes in sensor/patient relativeposition.

It can be appreciated that the use of the tonometric pressure sensor asthe basis for measurement of the physical parameter (as described indetail above with respect to the exemplary embodiment) provides thebenefits of both simplicity and reduced cost by eliminating the need foran added sensor or added complexity of the actuating mechanisms.However, certain benefits relating to the decoupling of the parametersignal from the arterial pressure signal (as compared to the use of thetonometric pressure signal as described above) may be realized throughuse of one of the alternate embodiments set forth above. For example,use of a non-hemodynamic parameter allows for the separation ofmechanical coupling changes from the physiologic signal, since no (or atleast minimal) physiologic content exists in the measurements obtainedin this fashion. Furthermore, the use of non-physiologic parameter(e.g., pad force or pressure as measured by the force on the applanationmotor shaft as described above) allows the use of a much smaller bufferzone, since there is effectively no overlap in the frequency andamplitude of the pressure signal as measured by the pad relative to thepressure changes induced by disruptions in mechanical coupling.

Description of Second Process

Referring now to FIGS. 2-2 i, one exemplary embodiment of the method ofidentifying changes in the compression coupling and readjustment of theapplanation level back to optimal (i.e., “second process”) according tothe invention is described in detail. It will be appreciated that whilethe following discussion of the exemplary embodiment is cast primarilyin terms of the adjustment of the tonometric applanation level (i.e.,level of compression), the techniques of the present aspect of theinvention may be equally applied to the other spatial domains associatedwith the tonometric measurement environment; e.g., lateral position andproximal position. Such applications may be coupled to that associatedwith the applanation domain, or alternatively be entirely independent.

It will also be appreciated that while the following discussion is castin terms of an exemplary embodiment utilizing Pseudo Random BinarySequences (PRBS) generally complying with a structured sequence of theform (2^(n)-1), other white noise, random/pseudo-random, or pseudo-noise(PN) processes may be substituted with success, and hence the followingdiscussion is merely illustrative of the broader principles of theinvention. For example, as one alternative, a pseudo-random generationalgorithm of the type well known in the communications arts (such asthat used for example in generating FHSS hop or CDMA pn “long code”sequences) is seeded with a given initial seed value and generates apseudo-random sequence, the latter used to modulate the applanationlevel in the present invention. Other perturbations or sequences (anymovement surrounding the optimal applanation position including forexample sinusoidal perturbations) may also be substituted consistentwith the present invention; however, the methods described with respectto the exemplary embodiment above have inherently good signal-to-noiseratio (SNR) across the frequency band of interest.

FIG. 2 shows a logical flow diagram of the exemplary embodiment of thesecond process 200. The process 200 generally comprises first providinga transducer adapted for determining pressure (step 202). The transduceris disposed proximate to the blood vessel of interest (step 204), inorder to provide coupling of pressure signals from the blood vessel wallthrough the tissue and to the active surface(s) of the sensor. Note thatan intermediary coupling agent (such as a gel) may be used if desired.Next, an optimal or near-optimal state of vessel compression is achievedper step 206. It will be recognized that such compression may be appliedvia the pressure transducer itself, or alternatively via anothermechanism (such as a contact pad). The optimized level of compressioncan be determined using, inter alia, the methods of the aforementionedco-pending U.S. patent application Ser. No. 10/072,508 filed Feb. 5,2002. The level of compression applied to the blood vessel is nextvaried over time (step 208). In the illustrated embodiment, the act ofvarying the level of compression per step 208 comprises modulating thelevel of compression in comparatively small magnitude “perturbations”according to a modulation sequence having particular desirableproperties, although other schemes (e.g., non-sequential) may be used.The effects of the modulation on the observed pressure values (e.g.,pulse pressure, diastolic, etc.) are then observed per step 210, andcorrections in the level of compression applied to the blood vessel madeper step 212 based on the observed effects of the modulation sequence.

It will be appreciated that the second process 200 (and associatedapparatus) need not measure the applied pressure or compression, such asvia a force sensor or the pressure transducer). Rather, the presentembodiment is largely effects-based in that applanation level(compression) can be adjusted based simply on the observed effects ofthe modulation. Hence, the applanation mechanism can advantageously bemade “dumb”, thereby simplifing the mechanism as well as other aspectsof the system. However, if explicit monitoring of the applied force orcompression is desired, such intelligence can be utilized in conjunctionwith the invention as well.

As previously discussed, one clinical objective of the second process200 is to maintain the tonometrically observed mean pressure within agiven value (e.g., +/−10 mmHg) of the optimum tonometric pressure, whichproduces maximum pulse pressure.

During the second process 200, both the patient's arterial pressure andthe mechanical coupling between the tonometric transducer and theunderlying artery can change. Either type of change introduces avariation in the tonometrically observed pressure. Hence, the presentinvention seeks to differentiate between physiologically-induced changes(e.g., those stemming from the patient's physiology, such as for exampledue to the introduction of pharmacological agents), and mechanicalcoupling changes in the tonometrically observed pressure. It also seeksto constantly correct for the second type of change (i.e., change in themechanical coupling).

Sudden changes in the mechanical coupling between the tonometricpressure transducer and the artery (i.e. acceleration or “bumping” ofthe transducer or the wrist) can be detected by several techniques, aspreviously described herein with respect to FIGS. 1, as well as that ofFIGS. 4-4 a described below. Slower changes in the mechanical couplingmust be detected and corrected by other means.

One method of detecting and correcting slower changes in mechanicalcoupling involves perturbing the system by modulating the compression ofthe artery and observing the resultant changes in tonometricallymeasured pulse pressure. The method and degree of perturbation should beoptimized in accordance with the overall clinical objectives.

Accordingly, the Assignee hereof has developed exemplary clinicalobjectives for use in accordance with the exemplary process 200described herein. It will be recognized that these objectives are merelyillustrative, and may be adapted and modified as needed to particularclinical environments or desired levels of performance and accuracy.

(i) Display disruption—First, the disruption of the system pressuredisplay by the induced perturbation should be minimized. Noticeablediscontinuities in the pressure display and delays in transfer of thepressure signal to the patient monitor (e.g., based on a predeterminedcriterion such as delays of 0.1 seconds or greater) are unacceptable.

(ii) Responsiveness—The tonometrically observed pressure from 20 mmHg ofoptimum T-Line pressure to within 10 mmHg occurs in accordance with agiven period of time (e.g., 1 minute). From a clinical perspective,excursions beyond roughly 10-15 mmHg in mean tonometrically measuredpressure from the actual intra-vascular pressure (such as A-Linepressure) for extended periods, e.g., longer than 1-2 minutes, are oftenclinically undesirable. Although measurement error can occur, asreflected by prevailing FDA requirements for cuff accuracy (+/−5 mmHgmean error with a standard deviation of 8 mmHg), more frequent andlonger duration divergences between tonometrically sensed pressure andtrue intravascular pressure reduce the clinical desirability of adevice. Thus, a clinically useful system should operate such that itresponds with reasonable speed and accuracy to changes in mechanicalcoupling.

(iii) Device Limitations—Limitations exist relating to the motion of theapplanation motor of the system. These limitations include for examplelimits in the applied electrical power and resulting output (mechanical)power and torque, the control of wear over time (i.e., motor longevity),and limits in the motor velocity and acceleration which precludeinstantaneous (i.e. step) changes in applanation. From bench dataobtained by Assignee, diastolic pressure in representative patientschanges on average 7 mmHg per 1000 motor steps (within the range of 4-10mmHg per 1000 motor steps) at an applanation level near optimum.Furthermore, pulse pressure changes for the same individuals an averageof 8 mmHg per 1000 motor steps (ranging from 4-14 mmHg per 1000 motorsteps). One exemplary actuator and motor scheme utilized by the Assigneehereof suggests a maximum rate of about 1000 motor steps per second.Changes in actuator design to alleviate some of these limitations arenot considered. Hence, it can be inferred that maximum rates ofdiastolic and pulse pressure change of about 7 mmHg/sec and 8 mmHg/sec,respectively, can be achieved with the aforementioned exemplaryapparatus.

(iv) Variations in Pulse Pressure—The patient's pulse pressure is timevariant. As is well documented in the literature, arrhythmias canproduce cyclical changes in pulse pressure (i.e. pulsusalternans,_wherein a succession of high and low pulses exist in such amanner that a low pulse follows regularly a high pulse, and this lowpulse is separated from the following high pulse by a shorter pause thanthat between it and the preceding high pulse.) See, e.g., “ApparentBigeminy and Pulsus Alterans in Intermittent Left Bundle-Branch Block”,Laszlo Littmann, M.D., and Jeffrey R. Goldberg, M.D., Departments ofInternal Medicine and Family Practice, Carolinas Medical Center,Charlotte, N.C., USA, which is incorporated by reference herein. It iswell documented that patient respiration can produce sizeable changes inpulse pressure as well. Hence, a perturbation and servo-control systemwould ideally be largely if not completely insensitive to cyclical andrandom fluctuations in arterial pulse pressure.

In addition to the foregoing objectives and limitations, the propertiesof the tonometric measuring and control system must be determined. It iswell known that the insertion of so-called “white noise” into a systemis a useful means of identifying properties associated with that system.In the present context, the introduction of such white noise generates apattern which effectively cannot be produced by the patient. physiology.The inputs to the system include applanation motor position, and the“system” is the tonometrically obtained pulse pressure as a function ofapplanation level. Cross-correlating the changes in applanation positioninduced by the white noise with the resultant observed pulse pressureproduces a relationship between the applanation motor position and pulsepressure. This relationship is advantageously quite robust in thepresence of random or periodic fluctuations in pulse pressure, duelargely to the insertion of the white noise.

However, several considerations exist with respect to the practicalimplementation of white noise modulation of applanation motor positionin the present invention. First, true “white noise” assumes a normal orGaussian distribution of motor position. Such normal distributions cancontain very large excursions from the mean albeit with increasinglyless frequency (theoretically not bounded), whereas in contrast themotor position in the physical implementation of the present inventionis bounded.

Second, the time to travel from one position limit to the other (if suchtravel is needed) is significant, as previously discussed with respectto maximum motor rate. Instantaneous changes in applanation mechanismposition are therefore not possible.

Third, white noise identification theoretically requires an infiniteperiod time for convergence, even approximations of which are notpractical in the clinical setting. Ideally, a useful clinical devicewould employ control systems which would converge in a very short periodof time, thereby enhancing the continuity of the tonometric pressuremeasurement.

As is known in the mathematical arts, Pseudo Random Binary Sequences(PRBS) are a defined sequence of inputs (+/−1) that possess correlativeproperties similar to white noise, but converge in within a give timeperiod. In addition, the inputs can be specified (and thereby optimized)to produce more effective signal-to-noise ratio (SNR) within theconstraints of the system. One common type of PRBS sequence generatoruses an n-bit shift register with a feedback structure containingmodulo-2 adders (i.e. XOR gates) and connected to appropriate taps onthe shift register. The generator generates a maximal length binarysequence of length (2^(n)-1). The maximal length (or “m-sequence”) hasnearly random properties that are particularly useful in the presentinvention, and is classed as a pseudo-noise (PN) sequence. Properties ofm-sequences commonly include:

(a) “Balance” Property—For each period of the sequence, the number of‘1’s and ‘0’s differ by at most one. For example in a 63 bit sequence,there are 32 ‘1’s and 31 ‘0’s.

(b) “Run Proportionality” Property—In the sequences of ‘1’s and of ‘0’sin each period, one half the runs of each kind are of length one, onequarter are of length two, one eighth are of length three, and so forth.

(c) “Shift and add” Property—The modulo-2 sum of an m-sequence and anycyclic shift of the same sequence results in a third cyclic shift of thesame sequence.

(d) “Correlation” Property—When a full period of the sequence iscompared in term-by-term fashion with any cyclic shift of itself, thenumber differences is equal to the number of similarities plus one (1).

(e) “Spectral” Properties—The m-sequence is periodic, and therefore thespectrum consists of a sequence of equally-spaced harmonics where thespacing is the reciprocal of the period. With the exception of the dcharmonic, the magnitude of the harmonics are equal. Aside from thespectral lines, the frequency spectrum of a maximum length sequence issimilar to that of a random sequence.

Accordingly, detecting and correcting slower-rate changes in mechanicalcoupling as previously described can be accomplished by applying PRBSmodulation of the applanation position, and observing the resultantchanges in tonometrically observed pulse pressure. In one exemplaryembodiment of the present invention, the physical implementation of sucha system contains three interactive “components”: (i) a modulator; (ii)a signal restoration entity; and (iii) an identification/servo controlentity. It will be recognized by those of ordinary skill that the term“entity” as used herein relates to any number of awide variety ofimplementations, ranging from a corporeal entity (e.g., electronics andassociated integrated circuits) to a completely virtual or intangibleone (e.g., one manifest in the form of algorithms, routines, or softwareobjects or components resident across the various hardware environmentsof a system).

The following exemplary description illustrates the operation of theaforementioned multi-component system according to one embodiment of theinvention.

Referring now to FIGS. 2 a-2 c, the characteristics and response of anexemplary patient are described. As shown in FIG. 2 a, the patientexhibits a given pulse pressure versus diastolic pressure relationship230. The maximum pulse pressure 232 (e.g., 42 mmHg in the illustratedexample) occurs at a diastolic pressure of about 75 mmHg 234.

Furthermore, it is assumed for purposes of illustration that theapplanation motor is held at a constant position (at the point ofoptimal compression corresponding to maximal pulse pressure), and thatthe patient has a time-invariant arterial pressure with a heart rate of60 bpm with the shape 236 shown in FIG. 2 b. If the patient's artery isnot sufficiently compressed, a lower diastolic pressure 237 (e.g.,diastolic pressure=67 mmHg in this example) will result, as indicated bythe “sub-optimal” waveform 238 of FIG. 2 c. Note that the pulse pressure(systolic minus diastolic) at a tonometrically measured diastolicpressure of 67 mmHg is only approximately 36 mmHg. Under this condition,the system must identify the fact that the artery is under-compressedand adjust the applanation level appropriately over time.

Referring now to FIGS. 2 d-2 e, the modulation entity of the servoprocess 200 of the invention is described in the context of theforegoing example. The modulator of the present embodiment introduceschanges in artery compression (applanation Position) over a limitedrange around the “optimal” operating point. These changes are in thepresent embodiment synchronized with the downward slope of the arterialpressure waveform, this downward slope being associated with diastolicrelaxation of the heart. Other synchronizations (or even lack ofsynchronization) may be used if desired, however. The modulationsinduced by the modulation entity ramp the applanation mechanism positionfrom one extreme to an equal and opposite extreme (e.g., 400 motor stepsin the present embodiment) around the operating point over a briefperiod (e.g., 0.5 seconds), although other profiles (symmetric ornon-symmetric) and durations may be substituted if desired. The decisionto move from one extreme to another is controlled in this embodiment bya Pseudo Random Binary Sequence (PRBS) of the type previously described.This modulation scheme produces changes in pressure offset, and mayproduce highly correlated changes in pulse pressure.

In the illustrated embodiment, a PRBS sequence of length=7 isimplemented (i.e., 1,1,1,−1,−1,1,−1) to modulate the pressure waveformas shown in FIG. 2 d. Note that for the clinical application, therespiratory period of the patient, and its corresponding cyclicalfluctuations in pulse pressure, approximates the repetition period ofthe PRBS of length 7. Hence, clinical embodiments of the applicationincorporate a PRBS of appropriate length such as length=15 (i.e., 1, 1,−1 ,1, −1, 1, 1, 1, 1, −1, −1, −1, 1, −1, −1) or length 31 (i.e.,1,1,1,1,−1,1,1,−1,−1, 1, 1, 1, −1, −1, −1, −1, 1, 1, −1, 1, −1, 1, −1,−1, 1, −1, −1, −1, 1, −1, 1) Specifically, the PRBS sequence repeatsevery 7, 15, 31 beats if one does not allow for transition beats, and inthe exemplary case 11, 22, or 47 beats respectively allowing fortransition beats. Any noise source that repeats in the same time base(sinusoidal noise frequency) will have a greater impact on systemperformance than noise sources with other frequency content. Respirationperiod occurs in the range of 5-7 seconds; hence, during this period,anywhere from 4-14 heartbeats could be observed. Thus, a PRBS sequenceof length 7 with an effective length 11 when transition beats areincluded falls directly within the respiration period. The longersequences do not have that problem. Conversely, however, the noiserejection properties require a complete cycle of data for properfunction. Hence, control using sequences that are excessively long areprone to sluggish control, thereby detracting from system performance.

FIG. 2 e depicts the practical implementation of PRBS changes inapplanation level. Practical mechanical considerations relating to theapplanation motor preclude step changes in applanation level ofsufficient magnitude to produce a significant change (e.g., 6 mmHg) inobserved tonometric pressure. Thus, for the present embodiment, theapplanation position is ramped over a period of time (e.g., 0.5seconds), as shown in the PRBS portion 239 of FIG. 2 e. Since noguarantee exists that the ramp will complete by the end of the beat, avariable delay in the PRBS, which is a function of heart rate and numberof motor steps traveled, is included within each transition periodwithout loss of the correlative properties. Typically this delay is 1heart beat. but at high heart rates could extend to two and possiblymore beats. It is noted that the PRBS portion 239 of FIG. 2 e isdimensionless. In effect, two classes of beats are created in thepresent implementation; “measurement” beats and “transition” beats. Whenthe motor is moved, transition beats are added (e.g., for a length=15sequence, 7 or 8 transition beats are added).

Referring now to FIGS. 2 e and 2 f, the signal restoration entity of theinvention is described in detail. As shown above, the modulation entitywill introduce changes in the measured pressure waveform. These changesin the pressure waveform may be disruptive to the clinician undercertain circumstances. Note that the PRBS-modulated pressure waveform240 of FIG. 2 e varies significantly around the tonometric pressure 242that would otherwise be observed if the PRBS or other modulation was notactive. Hence, the signal restoration entity must anticipate the changesin the observed tonometric pressure waveform introduced by themodulation entity, and (mathematically or otherwise) restore themodulated waveform to a shape that is clinically equivalent to theun-modulated tonometric waveform.

Specifically, by implementing a linear ramp during the period when themodulation is active, the original un-modulated waveform can berestored. This process assumes the amount of change that is observed bythe modulation is not large (e.g., <roughly 6 mmHg in the illustratedembodiment) and is adaptively identified (i.e., the cross-correlation ofthe PRBS modulation sequence and diastolic pressure from which theaverage diastolic pressure has been removed can be used to provide anestimate of the expected change in pressure produced by the modulation).

Note that the foregoing process in essence adds or subtracts a pressurecorrection offset to the measured pressure. When the modulation entailsextension of the sensor from the mechanism (in the exemplaryembodiment), the pressure offset correction is subtracted from themeasured pressure data, and vice-versa. The value (units in mmHg) of theoffset correction can not be directly determined unless compared with asource of true intravascular pressure (e.g., A-Line, thus defeating thepurpose of the tonometric sensor), but it can be estimated by evaluatingthe change in diastolic, systolic, mean, pulse, or similar pressurevalues correlated to the change in motor position. Thus, for example,the cross-correlation between the PRBS and the diastolic pressures (meanpressure removed) can be used to estimate the offset correction. Thisestimate can be updated with each new beat producing a continuousestimate of the offset correction. Note that during applanation motorramping, the offset correction of the exemplary embodiment also rampsfrom one extreme to the other. Additionally, it will be recognized thatthe amount of modulation (e.g., number of motor steps in the illustratedembodiment) can be adjusted to produce the desired amount of pressurechange. In the present embodiment, the modulation level is continuouslyadjusted to achieve 5 mmHg peak-to-peak excursion subject to a limit;i.e., provided that the peak-to-peak excursion is limited to between 50and 800 motor steps. Other modulation schemes and limits can be usedconsistent with the invention, however.

Note that lead/lag relating to the assumed start of the motor movement(as opposed to the actual start of movement), and the introduced changesin pressure, can lead to small artifacts or “bumps” in the pressurewaveform display; however, these are often imperceptible to theoperator, and advantageously no points of discontinuity exist in thedisplay, unlike prior art systems.

Errors between the actual and predicted pressure change (i.e., thosepredicted by the signal restoration entity relating to the appliedmodulation) are exhibited as small jitter synchronized with the PRBS inthe diastolic pressure display. FIG. 2 f depicts the “restored” waveform242; i.e., the waveform(s) of FIG. 2 e after correction by therestoration entity. Note that the error produced by the linear rampapproximation is small compared to both (i) the pulse pressure, and (ii)pixel resolution of the monitor. Thus, the process of restoring aclinically equivalent waveform is readily achieved using the techniquesdescribed herein.

Referring now to FIGS. 2 g-2 i, the identification/servo control (ISC)entity of the present embodiment is described.

As shown in FIG. 2 f, the corrected (“restored”) pulse pressure valuesassociated with points on the restored waveform 242 fluctuate aroundcorresponding ones of the nominal, non-modulated sub-optimal applanationwaveform 238. Further, it will be recognized that these fluctuations,albeit comparatively small in magnitude, generally correlate with themodulation in applanation level, as illustrated by FIG. 2 g.

The ISC entity of the present embodiment takes advantage of thecorrelative properties of white noise. As shown in FIG. 2 g, anauto-correlation of the PRBS modulation is performed. Theauto-correlation of the PRBS signal has a gain equal to the PRBS length(e.g., 7) for zero phase delay, and negative unity gain for other phasedelays until the PRBS repeats. The PRBS modulation, time synchronizedtonometrically measured pulse pressure, and un-corrected diastolicpressures for the preceding example are displayed in Table 2. Note thatthe PRBS values labeled “T” indicate transition beats where theapplanation motors are still in the process of ramping from one positionto the next. These beats are removed from the subsequentcross-correlation without loss of the correlative properties of thePRBS. TABLE 2 Un-Corrected Beat PRBS Pulse Pressure Diastolic Pressure 11 38 70 2 1 38 70 3 1 38 70 4 T 35 66 5 −1  34 64 6 −1  34 64 7 T 37 688 1 38 70 9 T 35 66 10 −1  34 64 11 T 37 68 12 1 38 70 13 1 38 70FIG. 2 h illustrates the weighted zero-mean values for pulse pressureand diastolic pressure (after removing the “transition” (T) beats) forthe first 7 beats, and synchronized to the PRBS modulation. It will benoted that the pulse pressure values 250 and diastolic pressure values252 are well correlated with the PRBS modulation of applanation level254.

Performing the cross-correlation between the PRBS modulation ofapplanation and the pulse and diastolic pressures produces a largesignal at phase delay=0, as shown in FIG. 2 i. For diastolic pressure,the change induced by the modulation equals 21 mmHg divided by the PRBSlength=21/7=3 mmHg. This means that the modulation process (extendingthe sensor out from operating point “0” during the modulation) caused a3 mmHg increase in diastolic pressure. The total excursion (fromPRB=“−1” to PRBS=“1” thus equals 6 mmHg (70 mmHg-64 mmHg) using thetable above. Similarly, the modulation-induced change in pulse pressureas shown in FIG. 2 i equals 14/7 or 2 mmHg. Thus, the system recognizesthat increasing compression (applanation) will increase the observedpulse pressure. Subsequently, the control system can change theoperating point (applanation motor position around which PRBS modulationoperates) appropriately to maintain optimal coupling. Using thisapproach, the control system can accurately track on a beat-by-beatbasis the motor position corresponding to the applanation level thatproduces maximum pulse pressure.

A circular buffer arrangement is used in the exemplary embodiment of theapparatus implementing the foregoing technique; this advantageouslyallows the calculation to be updated once per beat. It will berecognized, however, that other arrangements may be used to implementthe desired finctionality.

It will also be recognized that the techniques described above withrespect to the second process may be equally applied to the otherdomains of spatial variation; i.e., the lateral and/or proximal searchalgorithms with proper selection of random/pseudo-random sequence (e.g.,PRBS) parameters, thereby providing continuous tracking in the selecteddirection(s) as well as in the application domain. Such application andselection are readily implemented by those of ordinary skill given thepresent disclosure, and accordingly are not described further herein.

Based on observations and testing performed by the Assignee hereof, theperformance of the present invention may be further enhanced undercertain circumstances by the inclusion of one or more optional controland signal processing features; use of these features can enable thesystem to respond more quickly to an event by, inter alia, mitigatingcontrol overshoot and/or eliminating unwanted noise and other artifactsfrom the processed signals(s). These features include: (i) Hampelfiltering of pulse and diastolic pressures; (ii) the addition of aproportional component to the control (servo) loop; (iii) the adjustmentof integral control of the servo loop through estimation of the SNR; (v)increasing the precision of the diastolic cross-correlation; (vi)control of the initial settings for the diastolic pressurecross-correlation arrays; (vii) adjusting the integral gain based on theaverage pulse pressure; and (viii) correcting for BMI or other scalingartifact. Each of the foregoing features are now described in detail.

(i) Hampel Filter for Pulse and Diastolic Pressures—Improperly detectedbeats, noise, and cardiac arrhythmias can introduce large one-timechanges in pulse pressure measurements that are not reflective of theapplanation state of the patient. In the context of the second process200 described above, these beats can potentially disrupt the feedbackcontrol. One exemplary method of removing most of these beats comprisesindependently applying a Hampel filter of the type well known in thesignal processing arts to each of the positive PRBS pulse pressure andnegative PRBS pulse pressure values in the respective arrays. The Hampelfilter is advantageously employed as opposed to other filteringtechniques including low pass filters or median filters which increasethe time lag in the servo control loop.

(ii) Addition of Proportional Component to Servo Loop IntegralControl—The PRBS-based algorithm described above operates generally as asophisticated block filter with a lag equal to ½ of the PRBS length. Inthe second process 200, transition beats (PRBS length/2) are added tothe computation, thereby creating a lag (e.g., 11.25 beats in the aboveexample) from a change in coupling to its full impact to itsidentification through the cross-correlation with the PRBS andsubsequent servo control. This lag can produce an overshoot in theintegral servo control system when recovering from a manually introducedstep change in artery compression (such as may be experienced when theNIBP measurement apparatus is jarred), and the integral gain is set toolarge. Adding a proportional component to the servo control algorithmand retuning the integral control gain advantageously reduces themagnitude of this overshoot. Since the servo control system operatesbased on changes in the “target” applanation level, a proportionalcontrol component may take the form of Eqn. 4 below:M _(TP)(t)=K _(p)*(X _(corr) [t]−X _(corr) [t-k])  (Eqn. 4)where M_(TP)(t) is the new target applanation motor position, X_(corr)is the 0^(th) delay of the cross-correlation of the PRBS and zero meanpulse pressures, t is the current pulse, and k is the number of beatspast. In one exemplary embodiment, values of (k=3) and K_(p)=1×(integralgain) are utilized.

(iii) Integral Control of the Servo Loop by Estimating SNR—The non-zeroterms of the aforementioned cross-correlation provide some indication ofthe noise potentially present in the pulse pressure estimates. Adding a“governor” to the servo control system which is triggered upon attainingone or more predetermined criteria; e.g., when the non-zero terms(average absolute or maximum absolute) are a percentage of the 0^(th)term, can decrease the sensitivity of the system to such noise. Forexample, a manually introduced step change in artery compression canintroduce a large change in the operating state (see discussion of thefirst process 100 above), which can drive the initial recovery from theevent in the wrong direction until the aforementioned identification lagis overcome. Meanwhile, the non-zero elements of the cross correlationalso become large until the lag is also overcome. The governor mechanismdescribed herein mitigates the effects of these non-zero elements duringthe lag period.

(iv) Improved Precision on Diastolic Cross-Correlation—As describedabove with respect the “nominal” embodiment of the present invention,cross-correlations are performed between the diastolic pressure and thePRBS component. The accuracy of these cross-correlation calculations maybe increased by using the time varying signed modulation signal as thebasis of the cross-correlation, rather than the PRBS as previouslydescribed. When the signed modulation signal is implemented, thecross-correlation value is divided by the average absolute modulationsignal for the period under consideration; otherwise, the servoadjustment to subsequent modulation counts and operating applanationposition may be adversely impacted.

(v) Control of Initial Settings for Diastolic Pressure Cross-CorrelationArrays—To provide an initially reactive system and to speed initialconvergence, the nominal system is initialized to provide comparativelylarge modulations. On some patients, however, the modulation (measuredin the present context in terms of “motor delta” which is defined as theestimated absolute change in applanation motor position in stepsrequired to change end diastolic pressure by a pre-determined quantitysuch as 2.5 mmHg) is initially excessive; e.g., up to 8 or 10 times thenumber of motor steps otherwise required. If motor delta is set toolarge, then the applanation motor will initially move much farther thannecessary/desired during PRBS, and the patient's diastolic pressure willchange much greater than anticipated. Waveform reconstruction will notsufficiently compensate for changes in diastolic pressure, thus shiftsor oscillations in diastolic pressure will be noticeable on the pressuredisplay, which is undesirable. Nonetheless, the large motor delta willaid in the rapid convergence to the applanation position correspondingto maximum pulse pressure. On the contrary, if the motor delta is settoo small, then applanation will not sufficiently excite the system,thus slowing convergence to the applanation position corresponding tomaximum pulse pressure. Meanwhile, the restoration process willovercompensate for the change in diastolic pressure with PRBSmodulation, and produce noticeable shifting in the displayed pressure.

To address this issue, the initial modulation level can be controlled,such that a predetermined maximum number of steps (e.g., 150) areutilized, or alternatively by applying a more sophisticated technique ofdetermining the optimal initial modulation as illustrated in FIGS. 3-3b. Specifically, the initial applanation pressure sweep providessufficient data to estimate the necessary motor delta to changediastolic pressure by a predetermined amount (e.g., 2.5 mmHg). The sweepdata is first obtained (step 302 of FIG. 3), and is used to generate thearray of diastolic pressure data values, aiDiastoleP[ ], and the arrayof applanation position, alAppPos[ ], for all the beats in the sweep(step 304). At the end of the applanation sweep process, the beat whichprovided the maximum pulse pressure is identified as iSysPointer (step306).

In one exemplary embodiment of the method 300, outlying or abhorrentvalues are first removed from alAppPos[ ] and aiDiastoleP[ ] via aHampel filter of the type well known in the art, using for example a 3-or 4-standard deviations (σ) outlier test or comparable mechanism (step308). Other filter types can also be substituted, as will be appreciatedby those of ordinary skill.

Next, in step 310, those beats whose diastolic pressure ranges from thatassociated with the optimum beat minus a predetermined value (e.g., −10mmHg) to that corresponding to optimum beat plus the predetermined value(+10 mmHg) is determined.

The slope of the diastolic pressure/applanation position curve (in unitsof mmHg per motor step in the present embodiment) over that region ofinterest is next determined in step 312. This provides in effect asensitivity of diastolic pressure to motor position.

In step 314, the slope value(s) determined in step 312 are used tocalculate the number of applanation motor steps required to change thediastolic pressure by a desired amount (e.g., motor delta=2.5/slope inthe illustrated embodiment). In the illustrated embodiment, the PRBSprocess is simply a method of determining the slope around the nominal.

Lastly, in step 316, the motor delta value is bounded within acceptablelimits which will reduce initial “overstepping” of the modulation aspreviously described. For example, in one embodiment, the allowedinitial motor delta value is bounded on the low end by 40 motor steps,and on the high end by 400 motor steps.

It will also be recognized that a similar issue (i.e., “overstepping”)may arise when initiating an applanation sweep subsequent to the firstprocess 100 described above with respect to FIG. 1. Accordingly, theaforementioned methods of mitigating excessive modulations can beemployed in this context as well.

(vii) Gain Adjustment Based on Average Pulse Pressure—Adjustments tointegral gain (i.e., autocorrelation gain with zero phase delay) is inthe above-described embodiment independent of the underlying averagepulse pressure, as reflected in the following relationship:M _(TP)(t)=(K _(i) *K _(pp) [t]*K _(n) [t]*X _(corr) [t])+M_(TP)(t-1)  (Eqn. 5)where M_(TP)(t) is the new target applanation motor position,M_(TP)(t-1) is the previous target applanation motor position, X_(corr)is the 0^(th) delay of the cross-correlation of the PRBS and zero meanpulse pressures, t is the current pulse, K_(i) is the fixed integralgain, K_(pp)[t ] is the integral gain modifier that is inversely relatedto pulse pressure, and K_(n)[t] is the integral gain modifier that isrelated to the signal-to-noise ratio.

Thus, as an example, a pulse pressure cross-correlation of magnitude 2has the same control “impact” at an average pulse pressure of 60 mmHg asit does at 20 mmHg. Making the value of this gain quasi-inverselyproportional to the underlying average pulse pressure makes the controlsystem more responsive both for individuals with low pulse pressure, andfor all individuals when the system is not situated close optimum. Itwill be recognized that the foregoing coupling between the integral gainand pressure may take on other forms as well. For example, the gainadjustment need not be proportional or quasi-proportional, but rathermay be based on a limited number of continuous or non-continuousdiscrete pressure ranges if desired (e.g., 0-10 mmHg, >10-<25 mmHg,etc.), or made deterministic upon other measured or observed parameters.Furthermore, the gain adjustment may be coupled to underlying criteriaother than pulse pressure; e.g., diastolic or systolic pressure, meanpressure, blood flow velocity or kinetic energy, vessel diameter, bodymass index, etc.

(viii) Correction for Scaling on Observed Pressure Waveforms—Clinicalobservations made by the Assignee hereof indicate that under somecircumstances, limited changes in the pressure displayed to the operatormay be induced in part by the modulation occurring during the secondprocess 200 described above. One cause of this behavior relates to theinteraction of the pressure waveform restoration and scaling (e.g., BMI)algorithms with changing mean pressures. To address this behavior, analternate scaling implementation may be used. Specifically, thehigh-pass filter (HPF) component of the pressure waveform (2^(nd) order0.25 Hz cutoff frequency) is scaled, and combining the HPF componentmultiplied by the scaling factor (e.g., BMI scale factor) with the rawpressure waveform to produce the scaled pressure waveform.

It will be recognized that the foregoing features (i)-(viii) are purelyoptional in nature, and may be selected by the system designer at timeof apparatus design and manufacture based on the anticipatedapplications. Alternatively, production devices may incorporate thefunctionality for each enhancement (as well as others), with theend-user having the ability to select which features they wish to employin particular applications (such as via a GUI configuration menu, API,or similar mechanism).

As yet another alternative, the production device may be configured toautomatically or adaptively determine if particular performanceenhancements should be utilized. For example, during start-up ormonitoring, the device may be configured to institute or “turn on” agiven feature or group of features, monitor the effects on the outputdata in light of prior data collected while the enhancement feature(s)were inoperative, and then decide which if any features should beutilized and under what conditions. As a simple example, consider wherethe Hampel filter (Item (i) above) is applied over time to the PBRSpulse pressure at times where sudden change in values are expected(i.e., start or re-entrance into the servo control system). The systemmay be programmed to disable the Hampel filter during these periods ofservo control or during the period immediately following an ipsilateraloscillometric cuff deflation.

Hence, the present invention contemplates the use of innate“intelligence” within the device hardware and software adapted toselectively control the application of one or more enhancement featuresduring device operation. Such innate control can be readily implementedby those of ordinary skill given the present disclosure, and accordinglyare not described in greater detail herein.

Interaction of First and Second Processes

The first process 100 and second process 200 described above are in theexemplary embodiment adapted to operate in concert with each other. Asdiscussed, the first process 100 responds to sudden changes inmechanical coupling between tonometric sensor and the underlying arterywhile the second process is designed to, inter alia, counteract lowerfrequency drifting in the mechanical coupling. Generally speaking, themore quickly that the second process 200 can respond to changes inmechanical coupling, the less restrictive the constraints that areplaced on the performance of the first process 100. With the presence ofthe second process 200, the first process 100 need not be reactive tosmall mechanical coupling changes; the second process 200 can be used toprovide recovery without the need to disable current pressure displayfor any period of time to perform the limited pressure search.

Accordingly, the following comprise exemplary values for variousparameters used by the first and/or second processes of the invention,which are “tuned” so as to provide maximum efficiency and efficacy ofthe two processes when they are both present in a given system. It willbe readily apparent that other values (and in fact parameters) may besubstituted depending on the particular application(s) in which they areapplied.

(i) Tonometric Pressure Velocity and Acceleration Triggers used withfirst process 100:

-   POS_VEL_TRIGGER=45 mmHg:

(45 mmHg/3 samples)*(160 Sample/1 Second)=2400 mmHg/sec

-   NEG_VEL_TRIGGER=−20 mmHg:

(−20 mmHg/3 samples)*(160 Sample/1 Second)=−1067 mmHg/sec

-   POS_ACCL_TRIGGER=15 mmHg:

(15 mmHg/3 samples)*(160 Sample/1 Second²)=800 mmHg/sec²

-   NEG_ACCEL_TRIGGER=−12 mmHg:

(−12 mmHg/3 samples)*(160 Sample/1 Second²)=640 mmHg/sec²

-   MEAN_PRESSURE_CHANGE_TRIGGER=8 mmHg

(ii) Event trigger comparison of tonometric mean and pulse pressures offirst process 100:

PULSE_RANGE_PERCENT=10; a 10% decrease in decrease in tonometric pulsepressure triggers a limited pressure sweep (fourth state 105).

MEAN_RANGE_PERCENT=10; a 10% change in tonometric mean pressure and +/−8mmHg change in mean pressure triggers a limited pressure sweep (fourthstate 105).

Note that the second process 200 is in the exemplary embodiment madeactive when first process 100 is active in either the first state 102,second state 103, or third state 104 of the first process 100. TheAssignee hereof has also determined that under certain circumstances,scrubbing or elimination of the beats immediately surrounding a firstprocess event from use in the second process 200 may be helpful, sincethe measurement of mean pressure and pulse pressure for beatssurrounding the process event are corrupted.

Additionally, the exemplary embodiment renders the second process 200inactive when the first process 100 is active in its fourth state 105.The applanation motor position variable is set to the target positionupon entry into this fourth state 105, and the second process 200 isreinitialized upon return of the first process 100 from its fourth state105 to its first state 102.

The second process 200 can also be called from within the first process100 using any one of a number of well known software call routines inresponse to each new heart beat, and in concert with the previouslydescribed first process states 102-105 and initializations.

Additionally, the tonometric pressure velocity and acceleration triggers(i.e., POS_VEL_TRIGGER, NEG_VEL_TRIGGER, POS_ACCL_TRIGGER, andNEG_ACCEL_TRIGGER) associated with the first process 100 can beincreased to provide a larger buffer between normal physiologic changesin pressure and trigger levels, as follows: POS_VEL_TRIGGER=50 mmHg;NEG_VEL_TRIGGER=−25 mmHg; POS_ACCL_TRIGGER=20 mmHg; andNEG_ACCEL_TRIGGER=−15 mmHg.

Furthermore, the checks of beat-to-beat changes in mean pressurepreviously described with respect to the first process 100 may beeliminated when the two processes 100, 200 are used concurrently. Thesemean pressure checks are designed primarily for use as protectionagainst slow changes in mechanical coupling (via periodicsweep-calibration) when the first process 100 is used in a stand-aloneconfiguration (i.e., without the presence of the second process 200).The presence of the second process 200 obviates the need for thiscomponent, and thereby also possible false first process events causedby arrhythmias (i.e. pulsus alternans) and other physiologic events.

Concurrent use of the first and second processes 100, 200 alsoadvantageously allows more frequent use of “tuning” comparisons betweenpre- and post-event values of tonometrically measured mean and pulsepressures associated with the first process 100. This feature reducesthe frequency of periods where disabling or freezing of the display ofcurrent pressure is required to perform the limited applanation sweeps,by simply allowing the second process 200 to recover from these smallerchanges in mechanical coupling. Exemplary values are as follows:PULSE_RANGE_PERCENT=20; and MEAN_RANGE_PERCENT=20.

It will also be recognized that while the foregoing exemplary embodimentof the second process 200 is interactive with the first process 100, thesecond process may operate independently of the first. For example, thesecond process may be used to adjust and/or maintain the desiredapplanation level (or position in the case of lateral and proximalcases) irrespective of the methodology used to initially determine theoptimal applanation/position. In effect, the second process 200 of theinvention used without the first process 100 will hunt and eventuallyconverge on the optimal position itself. This approach, however, hasbeen found by the Assignee hereof to be less temporally efficient thanthe approach previously described (i.e., determining optimal using theinitial sweep process), but may none-the-less be desirable in certaincircumstances where hardware/software simplicity can be traded forlonger acquisition and settling times. Hence, the present inventionshould in no way be considered to be restricted to embodiments whereinboth first and second processes 100, 200 are employed.

Third Process

Referring now to FIGS. 4 and 4 a, the third process of the exemplaryembodiment of the present invention is described.

During patient monitoring mode, the second process 200 previouslydescribed is capable of controlling the applanation of the sensor/padagainst the subject artery and overlying tissue, thereby compensatingfor slow changes (drifts) in the mechanical coupling between thesensor/pad and the underlying tissue. Furthermore, the second process200 can be most effective over applanation ranges where the pulsepressure is strong (higher signal-to-noise ratio), which exist near theoptimal applanation position. However, for large shifts in themechanical coupling between sensor/pad and the tissue (i.e. flexing ofthe wrist), the second process 200 may require several miyutes toapplanate to the proper level to maximize tonometric pulse pressure.Thus, an opportunity exists to improve the performance of the system asa whole by detecting shifts in mechanical coupling that would incur anextended recovery period, and implement a more direct recovery process.The exemplary embodiment of the third process 400 shown in FIG. 4therefore takes a recovery “shortcut” as it were in those limitedcircumstances where recovery via the second process 200 would require anundesirably long time.

Thus, an important goal of the third process 400 of the presentinvention is to detect rapid shifts in mechanical coupling that inducesizeable error in pulse pressure and/or diastolic pressure, andimplement an optimal recovery approach.

In a first exemplary embodiment, the third process 400 is operated inconjunction with the first process 100 previously described.Specifically, the third process 400 operates during the first state 102of the first process 100 (see FIG. 1), and triggers the fourth state 105when an appreciable shift in the mechanical coupling is detected.Advantageously, the approach to detecting rapid shifts in couplingdescribed herein does not require any significant mechanical orelectrical changes to the system. The approach is based on identifyingchanges in tonometric pressure over a comparatively short period of timethat jointly are of the nature and degree to not likely occurphysiologically. Such changes also indicate that the second process 200might require significant time to properly recover. For example, when apatient's diastolic pressure increases, pulse pressure typically remainsconstant (or increases). Thus, detecting changes in pressure wherediastolic pressure increases and pulse pressure decreases significantlyover a short time period can be used to detect rapid shifts inmechanical coupling. Furthermore, episodes where the pulse pressureeither remains constant or increases are not problematic regardless ofthe change in diastolic pressure. Since the pulse pressure remains verystrong, the probability that the second process 200 can adjust theapplanation level (if necessary) within a reasonable period of timeremains high.

In the exemplary embodiment of FIG. 4, the process for detecting rapidshifts in mechanical coupling (third process 400) employs one or moremetrics for detecting joint shifts in parameters. In the illustratedembodiment, diastolic pressure and pulse pressure are used as thereferenced parameters, although it will be appreciated that otherparameters (physiologic or otherwise) may be substituted consistent withthe invention.

On exemplary scheme for detecting rapid shifts in mechanical coupling isdepicted in FIG. 4 a. The process 400 investigates changes in thecurrent block averaged pulse and diastolic pressures from “qualified”block averaged pulse and diastolic pressures from moving windows (e.g.,both 12 beats and 24 beats in the past in the illustrated embodiment).If the pulse pressure decreases and diastolic pressure deviates from theprevious diastolic pressures (12 or 24 beats past), then fourth state105 of the first process 100 is triggered.

Note that FIG. 4 a depicts a percentage change in pulse pressure (theselected parameter). Calculations may also be performed based uponchange in absolute blood pressure (mmHg), where for example 40 mmHg isequivalent to 100% and should trigger the fourth state 105 if either thepercent change or absolute change in pulse pressure in conjunction withthe change in diastolic pressure exceeds the prescribed thresholds. Itwill be recognized, however, that other triggering criteria and schemesmay be utilized if desired. Such alternate criteria and schemes may evenbe made specific to individual patient's or groups of patients, basedfor example on historical or anecdotal data or other indicia.

The operation of the exemplary embodiment of the rapid shift detectionalgorithm according to the present invention is now described in detail.As shown in FIG. 4, the algorithm of this embodiment is based upon thewaveform-restored but unscaled beat pressure diastolic and pulsepressure algorithms. The pulse pressure and diastolic beat pressure dataare in this embodiment processed through similar (yet not identical)parallel sub-processes to calculate current and past pressure data foruse in the aforementioned threshold determinations of the third process400. A primary difference between these two sub-processes is that in thefirst sub-process 440, drops in pulse pressure are of most concern,whereas in the second sub-process 442 changes in diastolic pressure areconsidered. Exemplary embodiments of these sub-processes 440, 442 arenow described in greater detail, although it will be appreciated thatother parameters (e.g., besides pulse pressure and diastolic pressure)may be used as the basis for rapid shift detection, and/or otherspecific configurations of these sub-processes may be substituted.

Furthermore, while the exemplary algorithms and functionality aredescribed in terms of first-in-first-out (FIFO) buffers, other bufferingarrangements may be utilized depending on the desired functionality fora given application. For example, under certain circumstances, it may bedesirable to replace portions of data in a LIFO (last-in-first-out)manner. Alternatively, “intelligent” (e.g., algorithmically driven)queuing and de-queuing of data may be incorporated. All such alternateapproaches are readily implemented by those of ordinary skill in thedata processing arts, and accordingly not described further herein.

-   i) Pulse Pressure Sub-process (Pre-filtering and Averaging)—The    following pre-filtering and averaging features are employed in the    exemplary embodiment of the first sub-process 440 used in analyzing    pulse pressure:

a. Hampel Filter—A Hampel filter (length 7) of the type previouslydescribed is used to remove abhorrent pulse pressure values fromsubsequent calculations, as shown in Eqn. 6 below. Note that aby-product of the exemplary Hampel Filter is the calculation of varianceamong the pulse pressures over the last 7 beats. This information isused subsequently to determine if the current pulse pressure should beincluded in the “acceptable” pulse pressure circular buffer.PP _(h)(k)=Hampel Filter{PP(k), PP(k-1), PP(k-2), . . . PP(k-6)}  (Eqn.6)where k represents the current beat number, PPh(k) is the Hampelfiltered pulse pressure, and PP(k) is the current unfiltered pulsepressure.

Furthermore, the Hampel filter of the present embodiment also calculatesthe variance of the data. The variance is a measure of distributionaround the mean. It is computed as the average squared deviation of eachnumber from its mean, as illustrated in Eqn. 7:PP _(var)(k)=((PP(k)-u)²+(PP(k-1)-u)² + . . . +((PP(k-6)-u)²/7,  (Eqn.7)where k represents the current beat number, PP_(var)(k) is the varianceof the pulse pressure over the last 7 beats, and u is the averageunfiltered pulse pressure for the last 7 beats.

b. Pulse Buffer—A pulse buffer (length=8 in the, exemplary embodiment)is a circular buffer containing the Hampel-filtered pulse pressurevalues. With each beat, the oldest beat is replaced with the most recentHampel-filtered data.

c. Block Average—A block averaging routine calculates the mean for theHampel-filtered pulse pressure data stored in the aforementioned pulsebuffer, as illustrated by Eqn. 8 below.PP _(h)(k)=[PP _(h)(k)+PP _(h)(k-1)+ . . . +PP _(h)(k-7)]/8  (Eqn. 8)where PP_(h)(k) is the block averaged Hampel filtered pulse pressuredata.

-   ii) Pulse Pressure Sub-process (Determining Current Pulse    Pressure)—The following features are utilized in the present    embodiment of the pulse pressure sub-process 440 for determining the    current pulse pressure:

a. Maximum—This feature of the algorithm determines the maximumdifference between the current pulse pressure and the block averagedHampel-filtered pulse pressure data, as shown below in Eqn. 9. Thismaximum is used in subsequent analysis as the Current Pulse Pressurevariable.If (PP _(h)(k)>PP _(h)(k))PP _(max) [k]=PP _(h)(k)Else PP _(max) [k]=PP _(h)(k)  (Eqn. 9)where PP_(max)[k] is used in subsequent comparisons to detect shifts inmechanical coupling. Note that the trigger for the fourth state 105 ofthe first process 100 is, in the illustrated embodiment, dependant on asignificant decrease in pulse pressure. Thus, under conditions where theaverage pulse pressure is small, the system should not trigger if thepulse pressure from the last beat is large.

-   iii) Pulse Pressure Sub-process (Determining Past Qualified Pulse    Pressures)—The following features are used in the present embodiment    for determining past (e.g., 12 & 24 beat) qualified pulse pressure    values.

a. Variance Buffer—In the exemplary embodiment, a variance buffer (e.g.,length=120) comprises a circular buffer containing the variance in thepulse pressure for the last “x” (e.g. 7) beats, as calculated withinHampel filter operation. With each beat, the data of the oldest beat isreplaced with the most recent variance.

b. Block Averager and Standard Deviation—These features calculate themean pressure for the variance in the Hampel filtered pulse pressuredata stored in the buffer, as illustrated in Eqns. 10 and 11 below,respectively. With the buffer length set at a comparatively large value(e.g., 120), these calculations provide a statistical benchmark fortypical average and range of variance observed for the blocks of pulsepressure data. Output of these algorithms is both block average andstandard deviation (or alternatively an equivalent measure that willenable detection of pulse pressures that are not within normal limits ofthe average mean pressure for the last number of beats n, where n=120 inthe present embodiment).PP _(var)(k)=[PP _(var)(k)+PP _(var)(k-1)+ . . . +PP_(var)(k-119)]/120  (Eqn. 10)where PP_(var)(k) is the block averaged Hampel filtered pulse pressuredata.SD _(PPvar)(k)=(((PP _(var)(k)-PP _(var)(k))²+(PP _(var)(k-1)-PP_(var)(k))²+ . . . +((PP _(var)(k-119)−PP _(var)(k))²)/120)^(1/2)  (Eqn.11)where SD_(PPvar)(k) is the standard deviation in the Pulse PressureVariance data.

c. Stationarity Limit—The stationary limit feature calculates an upperlimit of the pulse pressure variance or standard deviation that permitsthe current block (e.g., 7 beats) average pulse pressure to be includedin the history of “qualified” pulse pressure values for futurecomparisons. One exemplary approach comprises comparing the variance ofthe current pulse pressure block with the value (average pulsepressure+1 standard deviation of the variances observed over the last120 beats), which constitutes the upper limit of acceptable pulsepressures variance, as shown in Eqn. 12 below:StationarityLimit_(pp)(k)=PP _(var)(k)+SD _(PPvar)(k)  (Eqn. 12)Note, however, that other methods of determining an upper limit for theobserved variance may readily be substituted or used in conjunction withthe foregoing. For example, analysis of the current variance (e.g.,current variance <40^(th) largest out of 120 beats) may be utilized. Itwill be recognized that the aforementioned median filter can be easilymodified to recursively determine this value. Other configurations mayalso be employed consistent with the invention, such configurationsbeing readily determined by those of ordinary skill.

d. Identification of Pulse Pressure value to be included in PulsePressure History Buffer—The exemplary embodiment of the inventionfurther includes functionality which determines whether the currentaverage pulse pressure value or most recent acceptable pulse pressurevalue should be added to the circular buffer containing a history ofaverage pulse pressures, as shown in Eqn. 13 below. This is accomplishedusing the stationarity limit calculated previously.If (PP _(var)(k)>PP _(var)(k)+SD _(PPvar)(k))PPhistory(k)=PPhistory(k-1)Else PPhistory(k)=PP _(h)(k)  (Eqn. 13)where PPhistory(k) is the history of “acceptable” Pulse Pressures

e. Update Pulse Pressure History Buffer—In the exemplary embodiment, apulse pressure history FIFO buffer (e.g., length =24) is employed. Thehistory buffer comprises a circular buffer containing the history ofpast “acceptable” average pulse pressure values. With each beat, thedata associated with oldest beat is replaced with that of the mostrecent. Values which are a prescribed number of beats in the past (e.g.,12 and 24 beats) from this array are used in subsequent calculations todetermine the change in pulse pressure over this period.

-   iv) Diastolic Pressure Sub-process (Pre-filtering and    Averaging)—_The following pre-filtering and averaging features are    employed in the exemplary embodiment of the first sub-process 440    used in analyzing pulse pressure:

a. Hampel Filter—The exemplary embodiment of the diastolic sub-process442 uses a Hampel filter (e.g., length 7) to remove abhorrent diastolicpressure values from subsequent calculations, similar to the pulsepressure sub-process 440 (see Eqn. 14 below). A by-product of the HampelFilter is the calculation of the variance of diastolic-pressure over theprevious number (e.g., 7) of beats. This information is usedsubsequently to determine if the current diastolic pressure should beincluded in the “acceptable” diastolic pressure circular buffer.D _(h)(k)=Hampel Filter{D(k), D(k-1), D(k-2), . . . , D(k-6)}  (Eqn. 14)where k represents the current beat number, D_(h)(k) is the Hampelfiltered diastolic pressure, and D(k) is the current unfiltereddiastolic pressure. Furthermore, the Hampel filter also calculates thevariance of the data, as shown in Eqn. 15:D _(var)(k)=((D(k)-u)²+(D(k-1)-u)²+ . . . +((D(k-6)-u)²)/7,  (Eqn. 15)where k represents the current beat number, D,,(k) is the variance ofthe diastolic pressure over the last 7 beats, and u is the averagediastolic pressure over the last 7 beats.

b. Pulse Buffer—A FIFO pulse buffer of a determinate length (e.g.,length=8) is used in the present embodiment; this buffer comprises acircular buffer containing the Hampel filtered diastolic pressurevalues. With each successive beat, the data for the oldest beat isreplaced with the most recent Hampel filtered data.

c. Block Averager—A block averaging routine is used to calculate themean for the Hampel filtered diastolic pressure data stored in thebuffer, as shown in Eqn. 16 below:D _(h)(k)=[D _(h)(k)+D _(h)(k-1)+ . . . +D _(h)(k-7)]/8  (Eqn. 16)where D_(h)(k) is the block averaged Hampel filtered Diastolic pressuredata.

-   v) Diastolic Pressure Sub-process (Current Value Determination)—The    diastolic sub-process 442 determines the current value of the    diastolic pressure using a straightforward methodology.    Specifically, the current diastolic pressure is simply the most    recent block averaged Hamper-filtered diastolic pressure value. Note    that the trigger for the fourth state 105 of the first process 100    is dependant on a significant change in diastolic pressure.-   vi) Diastolic Pressure Sub-process (Determining Past Qualified    DiastolicPressures)—The sub-process 442 also contains mechanisms for    determining past qualified diastolic pressures (e.g., those of 12    and 24 beats past), as follows:

a. Variance Buffer—A FIFO variance buffer of determinate length (e.g.,length=120) comprising a circular buffer containing the variance in thediastolic pressure for the last 7 beats (as calculated within Hampelfilter operation) is used in the present embodiment of the diastolicsub-process 442. With each beat, the variance of the oldest beat isreplaced with the most recent variance.

b. Block Averager and Standard Deviation—These functions calculate themean for the variance in the Hampel-filtered diastolic pressure datastored in the Variance buffer. With the buffer length set at acomparatively large value, these calculations provide a statisticalbenchmark for the typical average and the range of variance observed forthe blocks of pulse pressure. Output from these processes is both blockaverage and standard deviation (or an equivalent measure) that willenable detection of pulse pressures that are not within normal limits ofthe average mean pressure for the last “n” beats), as shown in Eqns. 17and 18 below (for n=120):D _(var)(k)=[D _(var)(k)+D _(var)(k-1)+ . . . +D_(var)(k-119)]/120  (Eqn. 17)SD _(Dvar)(k)=(((D _(var)(k)−D _(var)(k))²+(D _(var)(k-1)-D _(var)(k))²+. . . +((D _(var)(k-119)-D _(var)(k))²)/119)^(1/2)  (Eqn. 18)where D_(var)(k) is the block averaged Hampel filtered diastolicpressure data.

c. Stationarity Limit—The stationary limit function of the diastolicsub-process 442 calculates an upper limit of the diastolic pressurevariance (or standard deviation) that permits the average diastolicpressure of the current block of data (e.g., 7 beats-worth) to beincluded in the history of diastolic pressure values for use in futurecomparisons, as shown in Eqn. 19:StationarityLimit_(D)(k)=D _(var)(k)+/−SD _(Dvar)(k)  (Eqn. 19)

d. Identify Diastolic Pressure value to be included in DiastolicPressure History Buffer—Using the stationarity limit previouslycalculated, this feature of the diastolic sub-process 442 determineswhether the current average diastolic pressure value or most recent“acceptable” diastolic pressure value should be added to the circularbuffer containing a history of average pulse pressures. If the newDiastolic Pressure is within limits of the stationarity limit describedabove, then it is included in the diastolic pressure history, else themost recent diastolic pressure history value is duplicated.

e. Update Diastolic Pressure History Buffer—In the exemplary embodiment,the diastolic subprocess 442 includes a circular FIFO buffer ofdeterminate length (e.g., length=24) containing the history of past“acceptable” average diastolic pressures. With each beat, the dataassociated with the oldest beat is replaced with that of the mostrecent. Values derived from one or more past beats (e.g., 12 and 24beats in the past from the current array) are used in subsequentcalculations to determine the change in pulse pressure over the periodof interest, as shown in Eqn. 20 below:If (D _(var)(k)>D _(var)(k)+SD _(Dvar)(k))Dhistory(k)=Dhistory(k-1)Else Dhistory(k)=⁻ D _(h)(k)  (Eqn. 20)

-   vii) Analysis for Detection of Shifts in Mechanical Coupling

a. Threshold detection—In order to detect rapid shifts in mechanicalcoupling, the third process 400 of the invention performs thresholddetection over the prior first number (e.g., 12) of beats in theexemplary embodiment as follows:

1) Pulse Pressure Difference—The third process 400 calculates thedifference between the current pulse pressure (Current Pulse Pressurevariable referenced with respect to Item ii.a. of the pulse pressuresub-process 440 above) and the first number (e.g., 12) of qualifiedpulse pressure beats in the past (stored in the circular history bufferby the pulse pressure sub-process 440 as previously described in iii.d.above). This calculation is shown in Eqn. 21 below:PulsePressureDifference12=PP _(max) [k]−PPhistory(12)  (Eqn. 21)

2) Diastolic Difference—The third process 400 calculates the differencebetween the current diastolic pressure (output from the diastolicsub-process block averager as described above) and the qualifieddiastolic pressure for, e.g., 12 beats in the past (stored in thecircular history buffer by the diastolic sub-process as described inItem vi.d. above), as shown in Eqn. 22:DiastolicPressureDifference12=D _(h)(k)−Dhistory(12)  Eqn. 22

3) Detector—In accordance with the temporal threshold shown in FIG. 4 a,if the pulse pressure difference (Item vii.a.1) above) is sufficientlynegative, and the diastolic pressure difference (Item vii.a.2) above) issufficiently different from zero, then a “Trigger 1” value 448associated with the fourth state 105 of the first process 100 is set toTRUE.

b. Additionally, the third process 400 of the invention performsthreshold detection over the prior second number (e.g., 24) of beats inthe exemplary embodiment as follows:

1) Pulse Pressure Difference—The third process 400 calculates thedifference between the current pulse pressure (Current Pulse Pressurevariable referenced above) and the qualified second number (e.g., 24) ofpulse pressure beats in the past (stored in the circular history bufferby the pulse pressure sub-process 440 as previously described), as shownin Eqn 23 below:PulsePressureDifference24=PP _(max) [k]−PPhistory(24)  (Eqn. 23)

2) Diastolic Difference: Calculates the difference between the currentdiastolic pressure (as previously described) and the qualified diastolicpressure 24 beats in the past, as illustrated by Eqn. 24 below:DiastolicPressureDifference24=D _(h)(k)−Dhistory(24)  (Eqn. 24)

3) Detector—In accordance with the temporal (e.g., 24 second) thresholdshown in FIG. 4 a, i the pulse pressure difference (Item vii.b.1) above)is sufficiently negative, and the diastolic pressure difference (Itemviii.b.2) above) is sufficiently different from zero, then the “Trigger2” value 450 for the fourth state 105 of the second process is set TRUE.

c. Beat Evaluation over Most Recent Period—Additionally, the thirdprocess 400 of the present invention is optionally configured toevaluate beats detected within a prior interval (e.g., prior fiveseconds), as follows:

1) No beat detected during interval—If a beat of acceptable quality hasnot been detected over the interval and “noise” on the pressure signalhas not caused the lack of a good beat, then the “Trigger 3” value 452for the fourth state 105 is set TRUE.

d. Fourth State Request Check—The third process 400 performs a logiccheck based on the presence of a Trigger 1, Trigger 2, or Trigger 3value 448, 450, 452 set to TRUE. If any of the aforementioned Triggersare set TRUE, and the first process 100 is in the first state 102, thenthe first process 100 should enter the fourth state 105 (i.e.,accelerated recovery). All fourth state Triggers 448, 450, 452 are thenreset to FALSE.

Note that if the first process 100 is in either the second state 103 orthird state 104, the proper new state option is subsequently determined.Alternatively, if the first process is currently in the fourth state105, then the aforementioned request to enter the fourth state 105 isignored.

It will be recognized that while the foregoing embodiment of the thirdprocess methodology addresses the problem of identifying rapid shifts inmechanical coupling based on a substantially probabilistic approach(which is tailored using an understanding of common changes in apatient's arterial pressure during the course of various physiologicevents), this approach does not measure directly (or even indirectly)changes in the mechanical coupling between the tonometric pressuresensor and its associated contact pad and the underlying tissue.Accordingly, the exemplary implementation of the third process 400 isnot immune to error. The second process 200 of the present invention,however, advantageously insulates the system against failure of thethird process 400 to detect rapid changes in coupling, since the secondprocess will converge on the optimal level of applanation irrespectiveof the third process (albeit over a period of several minutes) aspreviously described. Furthermore, false triggering by the third process400 (i.e., indication that a rapid coupling change has been experiencedwhen in fact it has not) will induce an applanation sweep, and possiblya lateral/proximal position sweep, which enables the system to recoveras well. Hence, any errors associated with the probabilisticimplementation of the third process 400 do not adversely affect theaccuracy of the system, but rather merely the speed with which itconverges on the proper applanation level and/or lateral or proximalposition. The exemplary embodiment of the present invention willtherefore not generate “bad” data, but rather simply not update datauntil optimal applanation/position is achieved.

It will also be noted that examination of a patient's data history asdescribed above with respect to the pulse pressure and diastolicsub-processes 440, 442 may encompass examinations of selected segmentsof the data history for that patient as well as the examination andcomparison of segments of data for that patient against comparable datafor other patients. Furthermore, the analysis described above may beapplied in both historical and/or predictive fashion; for instance, oneor more historical data segments may be analyzed via an algorithm whichpredicts future ranges or values for one or more parameters. If thesubsequent measurement of the parameter(s) is not within the prediction,instigation of the applanation/position sweep(s) can then conducted andthe optimal position reacquired. For example, wherein an analysis of thehistorical data for a patient relating to diastolic pressure indicatesthat a future measurement within a given time epoch r outside the rangeof 50-80 mmHg would correspond to an unphysical situation or event, anydiastolic pressure reading outside that range occurring within r couldtrigger reacquisition.

It will further be recognized that numerous combinations of analyzedparameters (e.g., systolic, diastolic, pulse, or mean pressure, andcombinations or derivations thereof), time periods (historical,historical/predictive, or purely predictive), and acceptance/rejectioncriteria (e.g., parameter range at a discrete epoch, continuity orvariation over time, statistics, etc.) may be utilized either alone orin combination consistent with the present invention to effectuate thegoal of maintaining optimal position of the sensor under all operatingenvironments and conditions. All such methods and approaches are readilyimplemented within the framework of the present invention by those ofordinary skill in the programming and mathematical arts, and accordinglyare not described further herein.

System Apparatus for Hemodynamic Assessment

Referring now to FIG. 5, an apparatus for measuring hemodynamicproperties within the blood vessel of a living subject is now described.In the illustrated embodiment, the apparatus is adapted for themeasurement of blood pressure within the radial artery of a human being,although it will be recognized that other hemodynamic parameters,monitoring sites, and even types of living organism may be utilized inconjunction with the invention in its broadest sense.

The exemplary apparatus 500 of FIG. 5 fundamentally comprises anapplanation assembly (including one or more pressure transducers 522)for measuring blood pressure from the radial artery tonometrically; adigital processor 508 operatively connected to the pressuretransducer(s) 522 (and a number of intermediary components) for (i)analyzing the signals generated by the transducer(s); (ii) generatingcontrol signals for the stepper motor 506 (via a microcontroller 511 aoperatively coupled to the stepper motor control circuits); and (iii)storing measured and analyzed data. The motor controllers 511, processor508, auxiliary board 523, and other components may be housed eitherlocally to the applanator 502, or alternatively in a separatestand-alone housing configuration if desired. The pressure transducer522 and its associated storage device 552 are optionally made removablefrom the applanator 502.

The pressure transducer 522 is, in the present embodiment, a strain beamtransducer element which generates an electrical signal in functionalrelationship (e.g., proportional) to the pressure applied to its sensingsurface 521, although other technologies may be used. The analogpressure signals generated by the pressure transducer 522 are convertedinto a digital form (using, e.g., an ADC 509) after being optionallylow-pass filtered 513 and sent to the signal processor 508 for analysis.Depending on the type of analysis employed, the signal processor 508utilizes its program either embedded or stored in an external storagedevice to analyze the pressure signals and other related data (e.g.,stepper motor position as determined by the position encoder 577,scaling data contained in the transducer's EEPROM 552 via I2C1 signal,need for reacquisition per FIG. 4, etc.).

As shown in FIG. 5, the apparatus 500 is also optionally equipped with asecond stepper motor 545 and associated controller 511 b, the secondmotor 545 being adapted to move the applanator assembly 502 laterallyacross the blood vessel (e.g., radial artery) of the subject asdescribed above. A third stepper motor (not shown) and associatedcontrols may also be implemented if desired to control the proximalpositioning of the applanation element 502. Operation of the lateralpositioning motor 545 and its controller 511 b is substantiallyanalogous to that of the applanation motor 506, consistent with themethodologies previously described herein.

As previously discussed, continuous accurate non-invasive measurementsof hemodynamic parameters (e.g., blood pressure) are highly desirable.To this end, the apparatus 500 is designed to (i) identify the properlevel of applanation of the subject blood vessel and associated tissue;(ii) continuously “servo” on this condition to maintain the bloodvessel/tissue properly biased for the best possible tonometricmeasurement; optionally (iii) scale the tonometric measurement as neededto provide an accurate representation of intravascular pressure to theuser/operator; and (iv) identify conditions where transient or“unphysical” events have occurred, and correct the system accordingly toregain the optimal applanation level and lateral/proximal positions.

During an applantion “sweep”, the controller 511 a controls theapplanation motor 506 to applanate the artery (and interposed tissue)according to a predetermined profile. Similarly, the extension andretraction of the applanation element 502 during the later states of thealgorithm (i.e., when the applanation motor 506 is disposed.at theoptimal applanation position, and subsequent servoing around this point)are controlled using the controller 511 a and processor 508. Such“servo” control schemes may also be employed with respect to the lateraland proximal motor drive assemblies if desired, or alternatively a morestatic approach (i.e., position to an optimal initial position, and thenreposition only upon the occurrence of an event causing significantmisalignment). In this regard, it will be recognized that the controlschemes for the applanation motor and the lateral/proximal positioningmotor(s) may be coupled to any degree desired consistent with theinvention.

The apparatus 500 is also configured to apply the methodologies of thefirst, second, and third processes 100, 200, 400 previously discussedwith respect to FIGS. 1-4, as well as the initial sweep and scalingmethodologies described in the aforementioned co-pending patentapplication Ser. No. 10/072,508 previously incorporated by referenceherein. Details of the implementation of these latter methodologies areprovided in the co-pending application, and accordingly are notdescribed further herein.

The physical apparatus 500 of FIG. 5 comprises, in the illustratedembodiment, a substantially self-contained unit having, inter alia, acombined pressure transducer 522 and applanation device 500, motorcontrollers 511, RISC digital processor 508 with associated synchronousDRAM (SDRAM) memory 517 and instruction set (including scaling lookuptables), display. LEDs 519, front panel input device 521, and powersupply 523. In this embodiment, the controllers 511 is used to controlthe operation of the combined pressure transducer/applanation device,with the control and scaling algorithms are implemented on a continuingbasis, based on initial operator/user inputs.

For example, in one embodiment, the user input interface comprises aplurality (e.g., two) buttons disposed on the face of the apparatushousing (not shown) and coupled to the LCD display 579. The processorprogramming and LCD driver are configured to display interactive promptsvia the display 579 to the user upon depression of each of the twobuttons.

Furthermore, a patient monitor (PM) interface circuit 591 shown in FIG.5 may be used to interface the apparatus 500 to an external orthird-party patient monitoring system. Exemplary configurations for suchinterfaces 591 are described in detail in co-pending U.S. patentapplication Ser. No. 10/060,646 entitled “Apparatus and Method forInterfacing Time-Variant Signals” filed Jan. 30, 2002, and assigned tothe Assignee hereof, which is incorporated by reference herein in itsentirety, although other approaches and circuits may be used. Thereferenced interface circuit has the distinct advantage of automaticallyinterfacing with literally any type of patient monitor system regardlessof its configuration. In this fashion, the apparatus 500 of the presentinvention coupled to the aforementioned interface circuit allowsclinicians and other health care professionals to plug the apparatusinto in situ monitoring equipment already on hand at their facility,thereby obviating the need (and cost) associated with a dedicatedmonitoring system just for blood pressure measurement.

Additionally, an EEPROM 552 is physically coupled to the pressuretransducer 522 as shown in FIG. 5 so as to form a unitary unit which isremovable from the host apparatus 500. The details of the constructionand operation of exemplary embodiments of such coupled assemblies aredescribed in detail in co-pending U.S. application Ser. No. 09/652,626,entitled “Smart Physiologic Parameter Sensor and Method”, filed Aug. 31,2000, assigned to the Assignee hereof, and incorporated by referenceherein in its entirety, although other configurations clearly may besubstituted. By using such a coupled and removable arrangement, both thetransducer 522 and EEPROM 552 may be readily removed and replaced withinthe system 500 by the operator.

It is also noted that the apparatus 500 described herein may beconstructed in a variety of different configurations, and using avariety of different components other than those specifically describedherein. For example, it will be recognized that while many of theforegoing components such as the processor 508, ADC 509, controller 511,and memory are described effectively as discrete integrated circuitcomponents, these components and their functionality may be combinedinto one or more devices of higher integration level (e.g., so-called“system-on-chip”(SoC) devices). The construction and operation of suchdifferent apparatus configurations (given the disclosure providedherein) are readily within the possession of those of ordinary skill inthe medical instrumentation and electronics field, and accordingly notdescribed further herein.

The computer program(s) for implementing the aforementioned first,second, and third processes (as well as scaling) are also included inthe apparatus 500. In one exemplary embodiment, the computer programcomprises an object (“machine”) code representation of a C⁺⁺ source codelisting implementing the methodology of FIGS. 1-4, either individuallyor in combination thereof. While C⁺⁺ language is used for the presentembodiment, it will be appreciated that other programming languages maybe used, including for example VisualBasicm, Fortran, and C⁺. The objectcode representation of the source code listing is compiled and may bedisposed on a media storage device of the type well known in thecomputer arts. Such media storage devices can include, withoutlimitation, optical discs, CD ROMs, magnetic floppy disks or harddrives, tape drives, or even magnetic bubble memory. These programs mayalso be embedded within the program memory of an embedded device ifdesired. The computer program may further comprise a graphical userinterface (GUI) of the type well known in the programming arts, which isoperatively coupled to the display and input device of the host computeror apparatus on which the program is run.

In terms of general structure, the program is comprised of a series ofsubroutines or algorithms for implementing the applanation and scalingmethodologies described herein based on measured parametric dataprovided to the host apparatus 500. Specifically, the computer programcomprises an assembly language/micro-coded instruction set disposedwithin the embedded storage device, i.e. program memory, of the digitalprocessor or microprocessor associated with the hemodynamic measurementapparatus 500. This latter embodiment provides the advantage ofcompactness in that it obviates the need for a stand-alone PC or similarhardware to implement the program's functionality. Such compactness ishighly desirable in the clinical and home settings, where space (andease of operation) are at a premium.

Method of Providing Treatment

Referring now to FIG. 6, a method of providing treatment to a subjectusing the aforementioned methods is disclosed. As illustrated in FIG. 6,the first step 602 of the method 600 comprises selecting the bloodvessel and location to be monitored. For most human subjects, this willcomprise the radial artery (as monitored on the inner portion of thewrist), although other locations may be used in cases where the radialartery is compromised or otherwise not available.

Next, in step 604, the applanation mechanism 502 is placed in the properlocation with respect to the subject's blood vessel. Such placement maybe accomplished manually, i.e., by the caregiver or subject by visuallyaligning the transducer and device over the interior portion of thewrist, by the pressure/electronic/acoustic methods of positioningpreviously referenced, or by other means. Next, the first applanationelement 502 is operated per step 606 so as to applanate the tissuesurrounding the blood vessel to a desired level so as to identify anoptimal position where the effects of transfer loss and other errorsassociated with the tonometric measurement are mitigated. Co-pending U.Spatent application Ser. No. 10/072,508 previously incorporated hereinillustrates one exemplary method of finding this optimum applanationlevel.

Once the optimal level of applanation for the applanator element 502 isset, the pressure waveform is measured per step 608, and the relevantdata processed and stored as required (step 610). Such processing mayinclude, for example, calculation of the pulse pressure (systolic minusdiastolic), calculation of mean pressures or mean values over finitetime intervals, and optional scaling of the measured pressurewaveform(s). One or more resulting outputs (e.g., systolic and diastolicpressures, pulse pressure, mean pressure, etc.) are then generated instep 612 based on the analyses performed in step 610. The relevantportions of the first, second, and third processes 100, 200, 400 of thepresent invention are then implemented as required to maintain thesubject blood vessel and overlying tissue in a continuing state ofoptimal or near-optimal compression (as well as maintaining optimallateral/proximal position if desired) per step 614 so as to providecontinuous monitoring and evaluation of the subject's blood pressure.This is to be distinguished from the prior art techniques and apparatus,wherein only periodic representations and measurement of intra-arterialpressure are provided.

Lastly, in step 616, the “corrected” continuous measurement of thehemodynarnic parameter (e.g., systolic and/or diastolic blood pressure)is used as the basis for providing treatment to the subject. Forexample, the corrected systolic and diastolic blood pressure values arecontinuously generated and displayed or otherwise provided to the healthcare provider in real time, such as during surgery. Alternatively, suchmeasurements may be collected over an extended period of time andanalyzed for long term trends in the condition or response of thecirculatory system of the subject. Pharmacological agents or othercourses of treatment may be prescribed based on the resulting bloodpressure measurements, as is well known in the medical arts. Similarly,in that the present invention provides for continuous blood pressuremeasurement, the effects of such pharmacological agents on the subject'sphysiology can be monitored in real time.

It is noted that many variations of the methods described above may beutilized consistent with the present invention. Specifically, certainsteps are optional and may be performed or deleted as desired.Similarly, other steps (such as additional data sampling, processing,filtration, calibration, or mathematical analysis for example) may beadded to the foregoing embodiments. Additionally, the order ofperformance of certain steps may be permuted, or performed in parallel(or series) if desired. Hence, the foregoing embodiments are merelyillustrative of the broader methods of the invention disclosed herein.

While the above detailed description has shown, described, and pointedout novel features of the invention as applied to various embodiments,it will be understood that various omissions, substitutions, and changesin the form and details of the device or process illustrated may be madeby those skilled in the art without departing from the spirit of theinvention. The foregoing description is of the best mode presentlycontemplated of carrying out the invention. This description is in noway meant to be limiting, but rather should be taken as illustrative ofthe general principles of the invention. The scope of the inventionshould be determined with reference to the claims.

1-68. (canceled)
 69. An apparatus for use in transient eventcompensation during hemodynamic parameter measurement from acompressible blood vessel, comprising: an applanation apparatus adaptedto establish an initial substantially optimal level of compression ofsaid blood vessel for at least a first epoch; a pressure sensor adaptedto measure pressure data from said blood vessel; and a computingapparatus having a computer program running thereon, said computerprogram adapted to receive pressure data from said pressure sensor anddetect the occurrence of a transient event by analyzing changes in saidpressure data, said transient event altering the mechanical couplingbetween said blood vessel and sensor; wherein said computing apparatusinitiates a pressure sweep to identify a second substantially optimallevel of compression based on said altered coupling; and wherein saidcomputing apparatus controls said applanation apparatus to establish thesecond substantially optimal level of compression of said blood vesselfor at least a second epoch.
 70. The apparatus of claim 69, wherein saidcomputer program waits for said transient event to subside beforeinitiating said sweep.
 71. The apparatus of claim 69, wherein saidinitiation of a pressure sweep by said computing apparatus comprises:utilizing said computer program to analyze pressure data relating to atleast two time periods occurring before and after said transient event,respectively; comparing changes in said pressure data from said at leasttwo time periods to a criterion; and sending a control signal to saidapplanation apparatus to initiate said pressure sweep when saidcriterion is satisfied.
 72. A continuous non-invasive blood pressuremeasurement system adapted for use on the radial artery of a livingsubject, comprising: a tonometric pressure sensor in contact with thetissue overlying said artery; a processing apparatus in signalcommunication with said sensor, said processing apparatus having acomputer program running thereon, said computer program adapted todetect at least one transient event using said blood pressure data;wherein in a first mode of operation of said system, blood pressure datais obtained using said sensor; and in a second mode of operationinitiated by said computer program, said system operates in a transientrecovery mode subsequent to said detection of said event.
 73. The systemof claim 72, wherein said first mode comprises a mode wherein a level ofcompression applied to said artery is varied in order to maintain saidartery in a substantially optimal state of compression for said act ofobtaining blood pressure data.
 74. The system of claim 73, wherein saidtransient recovery mode comprises a mode whereby a control signal issent from said computing apparatus to an applanation apparatus, saidcontrol signal causing said applanation apparatus to perform a sweepacross a plurality of levels of said compression of said artery in orderto reacquire said substantially optimal state.
 75. The system of claim73, wherein said compression of said artery is applied using saidsensor.
 76. A non-invasive blood pressure measurement system adapted foruse on the radial artery of a living subject, comprising: a tonometricpressure sensor in contact with the tissue at least partly overlyingsaid artery; a controller in signal communication with said sensor, saidcontroller having a first mode of operation, said first mode ofoperation being a non-transient mode wherein blood pressure data isobtained using said sensor, said controller being adapted to detect atleast one transient event during said act of obtaining said bloodpressure data; wherein said controller causes said system to operate,for at least a period of time, in a transient recovery mode subsequentto said detection of said event; and wherein said controller is furtheradapted to subsequently return said system to operation in saidnon-transient mode after completing said transient recovery mode.
 77. Anon-invasive hemodynamic measurement system, comprising: a pressuresensor adapted to measure pressure data originating from the artery of aliving subject; an applanation apparatus operatively coupled to saidpressure sensor; a controller in signal communication with said sensorand said applanation apparatus, said controller capable of (i) detectingat least one transient event within hemodynamic data obtained from saidsensor, and (ii) operating in a plurality of modes, said modescomprising; a first mode, wherein hemodynamic data is obtained from saidsensor; a second mode, entered subsequent to said detection of saidevent if said event does not have a first characteristic; and a thirdmode, entered subsequent to said detection if said event has said firstcharacteristic.
 78. The system of claim 77, wherein said firstcharacteristic comprises parameters indicating that said event is not(a) physiologic in origin, and (b) of sufficient magnitude that recoveryfrom said event in said second mode would exceed a first criterion. 79.The system of claim 77, wherein said second mode comprises a modeadapted to selectively vary a level of compression by said applanationapparatus via a control signal, wherein said varying level ofcompression is applied via said pressure sensor.
 80. The system of claim77, wherein said transient event comprises a motion initiated by asubject from which said hemodynamic data is being obtained, and saiddetecting comprises identifying at least one artifact within a waveformrelated to said hemodynamic data.
 81. The system of claim 80, whereinsaid identifying at least one artifact within a waveform related to saidhemodynamic data comprises detecting changes in a pressure waveformwhere diastolic pressure increases and pulse pressure decreasessignificantly over a given time period.
 82. The system of claim 80,wherein said identifying at least one artifact within a waveform relatedto said hemodynamic data comprises detecting changes in a first averagedpressure value with respect to a second averaged pressure value.
 83. Thesystem of claim 82, wherein said second average pressure value comprisesa value obtained from a moving cardiac beat window.
 84. A non-invasiveand continuous blood pressure measurement apparatus, comprising: anon-invasive pressure sensor coupled to an applanation apparatus, saidapplanation apparatus controlled at least in part by a computingapparatus adapted to collect hemodynamic data from said sensor, saidcomputing apparatus capable of operating in a plurality of modes, saidplurality of modes comprising: a first mode, wherein blood pressure datais obtained via said sensor from the circulatory system of a livingsubject; a second mode, wherein at least one transient event is detectedbased on said blood pressure data; and either a third mode subsequent tosaid detection of said event if said event is determined not to be ofsufficient severity that recovery from said event in said second modewould exceed a first criterion; or a fourth mode subsequent to saiddetection if said event is determined to be of sufficient severity thatrecovery from said event in said second mode would exceed said firstcriterion.
 85. The apparatus of claim 84, wherein said third modefurther comprises operating in said third mode only if said event isdetermined to originate from said circulatory system of said livingsubject.
 86. The apparatus of claim 84, wherein said fourth mode furthercomprises operating in said fourth mode only if said event is determinednot to originate from said circulatory system of said living subject.87. The apparatus of claim 84, wherein said first criterion comprises atime period or duration.
 88. The apparatus of claim 84, wherein saidevent comprises a movement of at least a portion of said apparatusrelative to said subject.
 89. The apparatus of claim 84, wherein saidevent comprises a movement of at least a portion of said apparatus andsaid subject.
 90. A pressure determining apparatus capable of operatingunder various transient conditions, comprising: a pressure sensoradapted to non-invasively measure pressure of a vessel; an applanationmechanism mechanically coupled to said pressure sensor; and a controllerapparatus in signal communication with said pressure sensor and saidapplanation mechanism, said controller apparatus having a computerprogram running thereon, said computer program capable of controllingsaid pressure determining apparatus under various transient conditions,said computer program comprising at least one functional unit adaptedto: determine a first substantially optimal initial level of compressionof a compressible vessel from which said pressure is measured; operatesaid apparatus at said first substantially optimal level of compressionfor at least a first epoch; detect the occurrence of a transient event;determine a second substantially optimal level of compression of saidvessel, said second level being different from said first level, saiddifference resulting at least in part from said transient event; andoperate said apparatus at said second substantially optimal level ofcompression for at least a second epoch, said first and second epochsoccurring at different times.
 91. The apparatus of claim 90, whereinsaid vessel comprises a blood vessel within the circulatory system of aliving subject.
 92. The apparatus of claim 90, wherein said vesselcomprises a pressure-containing vessel not within the circulatory systemof a living subject.
 93. A controller for use in a non-invasive pressuremonitoring apparatus, said controller being in signal communication withan applanation mechanism and a sensor, the controller comprising: afirst functional unit adapted to determine a first substantially optimalinitial level of compression for said blood vessel based at least inpart on pressure data originating from said sensor located proximatesaid blood vessel, said first functional unit being adapted to send afirst control signal to said applanation mechanism thereby operatingsaid applanation mechanism at said first substantially optimal level ofcompression for at least a first epoch; a second functional unit capableof detecting the occurrence of at least one sudden event; and a thirdfunctional unit adapted to determine a second substantially optimallevel of compression of said blood vessel, said second level beingdifferent from said first level, said difference resulting at least inpart from said at least one sudden event.
 94. The controller of claim93, wherein said first functional unit is capable of sending a secondcontrol signal to said applanation mechanism for operating at saidsecond substantially optimal level of compression for at least a secondepoch, said first and second epochs occurring at different times. 95.The controller of claim 93, wherein said detection of the occurrence ofat least one sudden event comprises detecting an externally-inducedtransient.
 96. The controller of claim 93, wherein said detection of theoccurrence of at least one sudden event comprises detecting asignificant change in the coupling between said sensor and said bloodvessel.
 97. The controller of claim 93, wherein said determination of asecond substantially optimal level comprises varying the applanationmechanism level of compression of said blood vessel over time, andevaluating blood pressure data obtained during said act of varying. 98.A non-invasive hemodynamic measurement system, comprising: anapplanation mechanism adapted to be controlled by a processingapparatus; and a hemodynamic sensor adapted to obtain hemodynamic datafor use by at least said processing apparatus; wherein said processingapparatus is adapted to operate the system in at least two modes, saidat least two modes comprising: a servo mode, wherein hemodynamic data isobtained by said system; and a transient recovery mode initiated by saidprocessing apparatus subsequent to the detection of at least onetransient event within said hemodynamic data, said transient recoverymode being adapted to promptly return said system to said servo mode.99. The apparatus of claim 98, wherein said obtaining hemodynamic datacomprises obtaining said hemodynamic data from a blood vessel, and saidtransient recovery mode comprises at least performing an applanationsweep of said blood vessel using said applanation mechanism.
 100. Anon-invasive hemodynamic measurement system, comprising: a non-invasivesensor adapted to obtain hemodynamic data; an applanation mechanism; anda controller apparatus, said controller apparatus in signalcommunication with said sensor and adapted to detect at least onetransient event within said hemodynamic data; wherein said hemodynamicdata is obtained in a non-transient mode of operation; and in atransient recovery mode entered into by said system subsequent to saiddetection of said event, a control signal generated by said controllercauses said applanation mechanism to modulate compression applied to ablood vessel from which said hemodynamic data is obtained.
 101. Thesystem of claim 100, wherein said modulation of compression by saidapplanation mechanism comprises modulating according to a substantiallyrandomized sequence.
 102. A non-invasive blood pressure measurementapparatus comprising: a pressure sensor; a data storage medium adaptedto store pressure data in a non-transient mode from said pressuresensor; and a processor adapted to detect the occurrence of at least onetransient event based at least in part on said data; wherein saidapparatus is placed in a transient recovery mode subsequent to saiddetection of said event.
 103. The apparatus of claim 102, wherein saidapparatus operates in a second non-transient mode when non-transientinduced changes occur, said non-transient changes being detected by saidprocessor by processing a second set of non-transient pressure data,said second set of non-transient pressure data obtained at least in partby modulating a compression level of a blood vessel with an applanationmechanism from which said non-transient data is obtained.